HAEM5:Plasma cell myeloma / multiple myeloma: Difference between revisions

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<blockquote class='blockedit'>{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Plasma Cell Myeloma]].
<blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Plasma Cell Myeloma]].
Other relevent pages include: [[HAEM4:Plasma Cell Myeloma Variants]]
Other relevent pages include: [[HAEM4:Plasma Cell Myeloma Variants]]


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<span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column to a table, click within the table and select the > symbol that appears to be given options. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])</span>
<span style="color:#0070C0">(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)</span>


==Primary Author(s)*==
==Primary Author(s)*==
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The University Of Texas MD Anderson Cancer Center, Department of Hematopathology, Houston, Texas
The University Of Texas MD Anderson Cancer Center, Department of Hematopathology, Houston, Texas
==WHO Classification of Disease==


__TOC__
{| class="wikitable"
 
!Structure
==Cancer Category / Type==
!Disease
 
|-
*[[Mature B Cell Neoplasm]] <ref name=":0">McKenna RW, et al., (2017). Plasma cell neoplasms, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p241-259.</ref>
|Book
 
|Haematolymphoid Tumours (5th ed.)
==Cancer Sub-Classification / Subtype==
|-
 
|Category
*Plasma cell neoplasms (PCNs) <ref name=":0" />
|B-cell lymphoid proliferations and lymphomas
 
|-
==Definition / Description of Disease==
|Family
 
|Plasma cell neoplasms and other diseases with paraproteins
 
|-
*A type of hematologic malignancy of monoclonal plasma cell
|Type
*Originated from bone marrow but affecting multiple tissues and organs
|Plasma cell neoplasms
*Hallmarks: presence of M protein, neoplastic plasma (myeloma) cells and sign(s) of end-organ damages (CRAB:  hypercalcemia, renal insufficiency, anemia and bone lesions)
|-
 
|Subtype(s)
 
|Plasma cell myeloma / multiple myeloma
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":0" /><ref name=":18">{{Cite journal|last=Chng|first=W. J.|last2=Dispenzieri|first2=A.|last3=Chim|first3=C.-S.|last4=Fonseca|first4=R.|last5=Goldschmidt|first5=H.|last6=Lentzsch|first6=S.|last7=Munshi|first7=N.|last8=Palumbo|first8=A.|last9=Miguel|first9=J. S.|date=2014-02|title=IMWG consensus on risk stratification in multiple myeloma|url=https://pubmed.ncbi.nlm.nih.gov/23974982|journal=Leukemia|volume=28|issue=2|pages=269–277|doi=10.1038/leu.2013.247|issn=1476-5551|pmid=23974982}}</ref><ref name=":10" /></blockquote>
|}
==Synonyms / Terminology==
 
*Multiple myeloma
*Medullary plasmacytoma
*Myelomatosis
*Myeloma, NOS
*Kahler disease (no longer used)
 
==Epidemiology / Prevalence==
 


*Plasma cell myeloma accounts for approximately 1% of all types of malignant tumors, 10-15% of all hematologic malignancies
==Related Terminology==
*It is the third most common hematologic malignancies, next to lymphoma and leukemia
*Incidence: 4 per 100,000 individuals per year
*It’s estimated that 34,920 adults (19,320 men and 15,600 women) will be newly diagnosed with plasma cell myeloma and 12,410 patients (6,840 men and 5,570 women) will die from this disease in the United States in 2021.
*It affects mostly adults with an age > 50 years (median age at diagnosis: 70 years). Young adults (<30 years) are infrequently and children (<16 years) are almost never affected by this disease.
*Male : Female ratio: 1.1 : 1
*Black : white ratio: 2 : 1
*Current 5-year relative survival rate:  54%


<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref>{{Cite journal|last=Kumar|first=Shaji K.|last2=Rajkumar|first2=Vincent|last3=Kyle|first3=Robert A.|last4=van Duin|first4=Mark|last5=Sonneveld|first5=Pieter|last6=Mateos|first6=María-Victoria|last7=Gay|first7=Francesca|last8=Anderson|first8=Kenneth C.|date=2017-07-20|title=Multiple myeloma|url=https://pubmed.ncbi.nlm.nih.gov/28726797|journal=Nature Reviews. Disease Primers|volume=3|pages=17046|doi=10.1038/nrdp.2017.46|issn=2056-676X|pmid=28726797}}</ref><ref name=":7">American Cancer Society, Cancer Facts & Figures 2020,https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2020.html</ref></blockquote>
==Clinical Features==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
{| class="wikitable"
{| class="wikitable"
|'''Signs and Symptoms'''
|+
|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
|Acceptable
 
|Myeloma; multiple myeloma (plasma cell myeloma) NOS
<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
 
<span class="blue-text">EXAMPLE:</span> Fatigue
 
<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
|-
|-
|'''Laboratory Findings'''
|Not Recommended
|<span class="blue-text">EXAMPLE:</span> Cytopenias
|N/A
 
<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
|}
|}


==Gene Rearrangements==


<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
*A wide spectrum of clinical presentations: from asymptomatic (e.g., smoldering plasma cell myeloma) to highly aggressive with end-organ damages (e.g., one of more of CRAB presentations)
*Bone pain can be the initial presentation in many cases
*Pale appearance due to anemia and sometimes bleeding
*Spinal cord compression due to vertebrae damages
*Peripheral neuropathy
*Infections due to compromised immunity can occur
*Organomegaly
*Skin lesions
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":0" /><ref name=":19">{{Cite journal|last=Rajkumar|first=S. Vincent|date=2016|title=Updated Diagnostic Criteria and Staging System for Multiple Myeloma|url=https://pubmed.ncbi.nlm.nih.gov/27249749|journal=American Society of Clinical Oncology Educational Book. American Society of Clinical Oncology. Annual Meeting|volume=35|pages=e418–423|doi=10.1200/EDBK_159009|issn=1548-8756|pmid=27249749}}</ref><ref name=":20">{{Cite journal|last=Moreau|first=Philippe|last2=Kumar|first2=Shaji K.|last3=San Miguel|first3=Jesús|last4=Davies|first4=Faith|last5=Zamagni|first5=Elena|last6=Bahlis|first6=Nizar|last7=Ludwig|first7=Heinz|last8=Mikhael|first8=Joseph|last9=Terpos|first9=Evangelos|date=2021-03|title=Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group|url=https://pubmed.ncbi.nlm.nih.gov/33662288|journal=The Lancet. Oncology|volume=22|issue=3|pages=e105–e118|doi=10.1016/S1470-2045(20)30756-7|issn=1474-5488|pmid=33662288}}</ref></blockquote>
</blockquote>
==Sites of Involvement==
*Bone marrow, multifocal or generalized
*Involvement of other organs and / or circulating plasma cells <ref>{{Cite journal|last=Granell|first=Miquel|last2=Calvo|first2=Xavier|last3=Garcia-Guiñón|first3=Antoni|last4=Escoda|first4=Lourdes|last5=Abella|first5=Eugènia|last6=Martínez|first6=Clara Mª|last7=Teixidó|first7=Montserrat|last8=Gimenez|first8=Mª Teresa|last9=Senín|first9=Alicia|date=06 2017|title=Prognostic impact of circulating plasma cells in patients with multiple myeloma: implications for plasma cell leukemia definition|url=https://pubmed.ncbi.nlm.nih.gov/28255016|journal=Haematologica|volume=102|issue=6|pages=1099–1104|doi=10.3324/haematol.2016.158303|issn=1592-8721|pmc=5451342|pmid=28255016}}</ref> may be secondarily but usually an indication of advanced disease ('''Is it ok? ~HM''')
*<s>Extramedullary sites: bones, kidney, upper airway, skin and so on.</s> ('''Extramedullary plasmacytoma is a different disease and it is closer to marginal zone lymphoma ~ HM''')
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":0" /><ref name=":19" /><ref name=":20" /></blockquote>
==Morphologic Features==
'''Radiology findings:''' <ref>{{Cite journal|last=Hillengass|first=Jens|last2=Usmani|first2=Saad|last3=Rajkumar|first3=S. Vincent|last4=Durie|first4=Brian G. M.|last5=Mateos|first5=María-Victoria|last6=Lonial|first6=Sagar|last7=Joao|first7=Cristina|last8=Anderson|first8=Kenneth C.|last9=García-Sanz|first9=Ramón|date=2019-06|title=International myeloma working group consensus recommendations on imaging in monoclonal plasma cell disorders|url=https://pubmed.ncbi.nlm.nih.gov/31162104|journal=The Lancet. Oncology|volume=20|issue=6|pages=e302–e312|doi=10.1016/S1470-2045(19)30309-2|issn=1474-5488|pmid=31162104}}</ref>
*Osteolytic lesions are detected in approximately 70% of plasma cell myeloma cases on radiology skeletal survey, MRI and PET/CT. Other presentation such as osteoporosis, pathological bone fracture, and vertebral compression fracture can be observed as well. Vertebrae, ribs, skull, shoulders, pelvis and long bones are the sites frequently affected with bone lesion(s).
'''Macroscopy findings:''' <ref name=":10" />
*During gross examination of severely affected bones, apparent defects filled with flesh-like hemorrhagic tissues can be observed.
'''Microscopy findings:''' <ref name=":18" /><ref name=":10" /><ref>{{Cite journal|last=Rajkumar|first=S. Vincent|last2=Dimopoulos|first2=Meletios A.|last3=Palumbo|first3=Antonio|last4=Blade|first4=Joan|last5=Merlini|first5=Giampaolo|last6=Mateos|first6=María-Victoria|last7=Kumar|first7=Shaji|last8=Hillengass|first8=Jens|last9=Kastritis|first9=Efstathios|date=2014-11|title=International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma|url=https://pubmed.ncbi.nlm.nih.gov/25439696|journal=The Lancet. Oncology|volume=15|issue=12|pages=e538–548|doi=10.1016/S1470-2045(14)70442-5|issn=1474-5488|pmid=25439696}}</ref>
*Plasma cells in plasma cell myeloma can show mature and immature (or plasmablastic) forms. <ref>{{Cite journal|last=Handa|first=U.|last2=Chhabra|first2=S.|last3=Mohan|first3=H.|date=2010-06|title=Plasma cell tumours: cytomorphological features in a series of 12 cases diagnosed on fine needle aspiration cytology|url=https://pubmed.ncbi.nlm.nih.gov/19416310|journal=Cytopathology: Official Journal of the British Society for Clinical Cytology|volume=21|issue=3|pages=186–190|doi=10.1111/j.1365-2303.2009.0641.x|issn=1365-2303|pmid=19416310}}</ref>
*The mature plasma cells usually have eccentric nuclei, dense "clock face" chromatin, and abundant, deep basophilic (on Wright Giemsa stained marrow or cytological preparations) or amphophilic (on hematoxylin and eosin-stained histological sections) cytoplasm with a paranuclear hof.
*Histologically, the monotypic plasma cells may present as interstitial, scattered distribution, in a form of small clusters and/or focal nodules. In advanced disease stages, the neoplastic plasma cells proliferate as diffuse sheets and replace normal bone marrow. <ref name=":0" />
'''Here I kept more detailed morphology descriptions ~HM'''
'''Differential diagnosis considerations may include:'''
*Lymphoplasmacytic lymphoma (LPL, related to Waldenstrom macroglobulinemia, WM) and splenic/nodal marginal zone lymphoma can have extensive monotypic plasmacytic differentiation.
*Mantle cell lymphoma (MCL) and a subset of plasma cell myeloma can share expressions of Cyclin D1 (''CCND1'') due to t(11;14)(q13;q32)(''IGH''/''CCND1'') translocation.
*In the setting of plasmablastic morphology, differential diagnosis includes: anaplastic plasma cell myeloma, plasmablastic lymphoma, primary effusion lymphoma (PEL), ALK-positive large B-cell lymphoma, immunoblastic diffuse large B-cell lymphoma, and HHV8-positive diffuse large B-cell lymphoma NOS. <ref>{{Cite journal|last=Harmon|first=Charles M.|last2=Smith|first2=Lauren B.|date=2016-10|title=Plasmablastic Lymphoma: A Review of Clinicopathologic Features and Differential Diagnosis|url=https://pubmed.ncbi.nlm.nih.gov/27684979|journal=Archives of Pathology & Laboratory Medicine|volume=140|issue=10|pages=1074–1078|doi=10.5858/arpa.2016-0232-RA|issn=1543-2165|pmid=27684979}}</ref>
*Non-hematopoietic neoplasms with plasmacytoid morphology can also mimic plasma cell myeloma, such as plasmacytoid myoepithelioma of minor salivary glands <ref>{{Cite journal|last=Santos|first=Esaú P.|last2=Cavalcante|first2=Danielle Rr|last3=Melo|first3=Allan Uc|last4=Pereira|first4=José C.|last5=Gomes|first5=Margarete Z.|last6=Albuquerque|first6=Ricardo Lc|date=2011-12-12|title=Plasmacytoid myoepithelioma of minor salivary glands: report of case with emphasis in the immunohistochemical findings|url=https://pubmed.ncbi.nlm.nih.gov/22152025|journal=Head & Face Medicine|volume=7|pages=24|doi=10.1186/1746-160X-7-24|issn=1746-160X|pmc=3285037|pmid=22152025}}</ref>, medullary thyroid carcinoma (or other neuroendocrine tumors) <ref>{{Cite journal|last=Mehdi|first=Ghazala|last2=Maheshwari|first2=Veena|last3=Ansari|first3=Hena A.|last4=Sadaf|first4=Lubna|last5=Khan|first5=Mohammad Amanullah|date=2010-04|title=FNAC diagnosis of medullary carcinoma thyroid: A report of three cases with review of literature|url=https://pubmed.ncbi.nlm.nih.gov/21157553|journal=Journal of Cytology|volume=27|issue=2|pages=66–68|doi=10.4103/0970-9371.70745|issn=0974-5165|pmc=3001179|pmid=21157553}}</ref>, and melanoma. It is important to keep in mind that CD138 is positive in many normal and neoplastic epithelial cells.
==Immunophenotype==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Finding!!Marker
!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|-
|Positive (universal)||<span class="blue-text">EXAMPLE:</span> CD1
|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)
|<span class="blue-text">EXAMPLE:</span> Common (CML)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
|<span class="blue-text">EXAMPLE:</span>
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference).
|-
|-
|Positive (subset)||<span class="blue-text">EXAMPLE:</span> CD2
|<span class="blue-text">EXAMPLE:</span> ''CIC''
|-
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
|Negative (universal)||<span class="blue-text">EXAMPLE:</span> CD3
|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
|<span class="blue-text">EXAMPLE:</span> D
|
|<span class="blue-text">EXAMPLE:</span>
 
''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
|-
|-
|Negative (subset)||<span class="blue-text">EXAMPLE:</span> CD4
|<span class="blue-text">EXAMPLE:</span> ''ALK''
|}
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''




<blockquote class='blockedit'>{{Box-round|title=v4:Immunophenotype|The content below was from the old template. Please incorporate above.}}
Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
 
|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
<br />
|<span class="blue-text">EXAMPLE:</span> N/A
 
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
*'''Plasma cell identification''': For flow cytometry immunophenotyping, benign and neoplastic plasma cells can be identified with combined use of CD38 and CD138. <ref>{{Cite journal|last=Rawstron|first=A. C.|last2=Orfao|first2=A.|last3=Beksac|first3=M.|last4=Bezdickova|first4=L.|last5=Brooimans|first5=R. A.|last6=Bumbea|first6=H.|last7=Dalva|first7=K.|last8=Fuhler|first8=G.|last9=Gratama|first9=J.|date=2008|title=Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders|url=http://www.haematologica.org/cgi/doi/10.3324/haematol.11080|journal=Haematologica|language=en|volume=93|issue=3|pages=431–438|doi=10.3324/haematol.11080|issn=0390-6078}}</ref> However, since anti-CD38 monoclonal antibodies (such as daratumumab) are used in myeloma therapy regimens, <ref>{{Cite journal|last=Palumbo|first=Antonio|last2=Chanan-Khan|first2=Asher|last3=Weisel|first3=Katja|last4=Nooka|first4=Ajay K.|last5=Masszi|first5=Tamas|last6=Beksac|first6=Meral|last7=Spicka|first7=Ivan|last8=Hungria|first8=Vania|last9=Munder|first9=Markus|date=2016-08-25|title=Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma|url=https://pubmed.ncbi.nlm.nih.gov/27557302|journal=The New England Journal of Medicine|volume=375|issue=8|pages=754–766|doi=10.1056/NEJMoa1606038|issn=1533-4406|pmid=27557302}}</ref> the expression of CD38 on the residual myeloma cells can be decreased or negative on the marrow cells. It should be noted that plasma cells lose surface CD138 overtime after specimen procurement (such as from bone marrow aspirates); <ref name=":14">{{Cite journal|last=Lin|first=Pei|last2=Owens|first2=Rebecca|last3=Tricot|first3=Guido|last4=Wilson|first4=Carla S.|date=2004|title=Flow Cytometric Immunophenotypic Analysis of 306 Cases of Multiple Myeloma|url=http://ajcp.metapress.com/openurl.asp?genre=article&id=doi:10.1309/74R4-TB90-BUWH-27JX|journal=American Journal of Clinical Pathology|volume=121|issue=4|pages=482–488|doi=10.1309/74R4-TB90-BUWH-27JX|issn=0002-9173}}</ref><ref>{{Cite journal|last=Kumar|first=Shaji|last2=Kimlinger|first2=Teresa|last3=Morice|first3=William|date=2010-09|title=Immunophenotyping in multiple myeloma and related plasma cell disorders|url=https://pubmed.ncbi.nlm.nih.gov/21112041|journal=Best Practice & Research. Clinical Haematology|volume=23|issue=3|pages=433–451|doi=10.1016/j.beha.2010.09.002|issn=1532-1924|pmc=3005703|pmid=21112041}}</ref> therefore, delayed specimen processing will cause underestimated plasma cell percentage in flow cytometry immunophenotyping and lower yield in CD138 enrichment of plasma cell for cytogenetic studies. For immunohistochemical studies on Formalin-Fixed Paraffin-Embedded (FFPE) tissue sections, CD138 and MUM-1/IRF4 can be used to identify plasma cells.
|<span class="blue-text">EXAMPLE:</span> T
*'''Myeloma plasma cells''': Unlike non-neoplastic plasma cells or plasma cells differentiated from lymphomas (especially marginal zone lymphoma and lymphoplasmacytic lymphoma), myeloma plasma cells often show aberrant loss of CD19 and CD45; they may also aberrantly express CD56, CD117, and/or Cyclin D1, which is associated with IGH/CCND1 translocation. For common aberrant immunophenotype patterns for myeloma cells, please see Flores-Montero et al. <ref name=":8">{{Cite journal|last=Flores-Montero|first=Juan|last2=de Tute|first2=Ruth|last3=Paiva|first3=Bruno|last4=Perez|first4=José Juan|last5=Böttcher|first5=Sebastian|last6=Wind|first6=Henk|last7=Sanoja|first7=Luzalba|last8=Puig|first8=Noemí|last9=Lecrevisse|first9=Quentin|date=2016|title=Immunophenotype of normal vs. myeloma plasma cells: Toward antibody panel specifications for MRD detection in multiple myeloma: MM MRD ANTIBODY PANELS|url=http://doi.wiley.com/10.1002/cyto.b.21265|journal=Cytometry Part B: Clinical Cytometry|language=en|volume=90|issue=1|pages=61–72|doi=10.1002/cyto.b.21265}}</ref> The aberrancy of immunophenotypes of myeloma plasma cells can be used for minimal/measurable residual disease (MRD) detection in myeloma.  <ref>{{Cite journal|last=Flores-Montero|first=J|last2=Sanoja-Flores|first2=L|last3=Paiva|first3=B|last4=Puig|first4=N|last5=García-Sánchez|first5=O|last6=Böttcher|first6=S|last7=van der Velden|first7=V H J|last8=Pérez-Morán|first8=J-J|last9=Vidriales|first9=M-B|date=2017|title=Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma|url=http://www.nature.com/articles/leu201729|journal=Leukemia|language=en|volume=31|issue=10|pages=2094–2103|doi=10.1038/leu.2017.29|issn=0887-6924|pmc=PMC5629369|pmid=28104919}}</ref><ref>{{Cite journal|last=on behalf of the EuroFlow Consortium (EU-FP6, LSHB-CT-2006-018708)|last2=Kalina|first2=T|last3=Flores-Montero|first3=J|last4=van der Velden|first4=V H J|last5=Martin-Ayuso|first5=M|last6=Böttcher|first6=S|last7=Ritgen|first7=M|last8=Almeida|first8=J|last9=Lhermitte|first9=L|date=2012|title=EuroFlow standardization of flow cytometer instrument settings and immunophenotyping protocols|url=http://www.nature.com/articles/leu2012122|journal=Leukemia|language=en|volume=26|issue=9|pages=1986–2010|doi=10.1038/leu.2012.122|issn=0887-6924|pmc=PMC3437409|pmid=22948490}}</ref><ref>{{Cite journal|displayauthors=1|last=B|first=Paiva|last2=N|first2=Puig|last3=Mt|first3=Cedena|last4=L|first4=Rosiñol|last5=L|first5=Cordón|last6=Mb|first6=Vidriales|last7=L|first7=Burgos|last8=J|first8=Flores-Montero|last9=L|first9=Sanoja-Flores|date=2020|title=Measurable Residual Disease by Next-Generation Flow Cytometry in Multiple Myeloma|url=https://pubmed.ncbi.nlm.nih.gov/31770060/|journal=J Clin Oncol|language=en|volume=38|pages=784-792|pmid=31770060|via=}}</ref>
|
*'''Monoclonality''': confirmed by immunoglobulin (Ig) light chain analysis, presenting as monotypic cytoplasmic immunoglobulin (cIg) expression but lack surface immunoglobulin (sIg). <ref name=":14" /> On FFPE tissue sections, immunoglobulin light chain analysis on plasma cells can be assessed either by immunohistochemical stains or by chromogenic in situ hybridization (CISH).
|<span class="blue-text">EXAMPLE:</span>
 
<br />
</blockquote>
==Chromosomal Rearrangements (Gene Fusions)==
 
Put your text here and fill in the table


{| class="wikitable sortable"
Both balanced and unbalanced forms are observed by FISH (add references).
|-
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
|<span class="blue-text">EXAMPLE:</span> ''ABL1''
!Diagnostic Significance (Yes, No or Unknown)
|<span class="blue-text">EXAMPLE:</span> N/A
!Prognostic Significance (Yes, No or Unknown)
|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
!Therapeutic Significance (Yes, No or Unknown)
|<span class="blue-text">EXAMPLE:</span> N/A
!Notes
|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|
|-
|-
|<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)||<span class="blue-text">EXAMPLE:</span> 3'ABL1 / 5'BCR||<span class="blue-text">EXAMPLE:</span> der(22)||<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
|
<span class="blue-text">EXAMPLE:</span> 30% (add reference)
|
|Yes
|
|No
|
|Yes
|
|<span class="blue-text">EXAMPLE:</span>
|
|
|
|}


The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
|}


 
<blockquote class="blockedit">{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
* Chromosomal Rearrangements (Gene Fusions)
* Chromosomal Rearrangements (Gene Fusions)
* Individual Region Genomic Gain/Loss/LOH
* Individual Region Genomic Gain/Loss/LOH
* Characteristic Chromosomal Patterns
* Characteristic Chromosomal Patterns
* Gene Mutations (SNV/INDEL)}}
* Gene Mutations (SNV/INDEL)}}</blockquote>




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'''Gene mutation'''s are also helpful for risk stratification in  plasma cell myeloma, e.g., mutations of IRF4 or PRDM1 genes involving plasma cell differentiation are usually indicative for a favorable prognosis, while mutation of ''TP53'', ''ATM'' or ''ATR'' genes involving DNA repair pathway mostly imply for a poor prognosis. <ref name=":11" />   
'''Gene mutation'''s are also helpful for risk stratification in  plasma cell myeloma, e.g., mutations of IRF4 or PRDM1 genes involving plasma cell differentiation are usually indicative for a favorable prognosis, while mutation of ''TP53'', ''ATM'' or ''ATR'' genes involving DNA repair pathway mostly imply for a poor prognosis. <ref name=":11" />   


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Individual Region Genomic Gain / Loss / LOH==
==Individual Region Genomic Gain/Loss/LOH==


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable. Do not delete table.'') </span>


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
!Diagnostic Significance (Yes, No or Unknown)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Prognostic Significance (Yes, No or Unknown)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Therapeutic Significance (Yes, No or Unknown)
!Clinical Relevance Details/Other Notes
!Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
7
7
|<span class="blue-text">EXAMPLE:</span> Loss
|<span class="blue-text">EXAMPLE:</span> Loss
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
 
chr7
chr7:1- 159,335,973 [hg38]
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
 
Unknown
chr7
|<span class="blue-text">EXAMPLE:</span> D, P
|Yes
|<span class="blue-text">EXAMPLE:</span> No
|Yes
|No
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
 
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references).
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
8
8
|<span class="blue-text">EXAMPLE:</span> Gain
|<span class="blue-text">EXAMPLE:</span> Gain
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
 
chr8
chr8:1-145,138,636 [hg38]
|<span class="blue-text">EXAMPLE:</span>
Unknown
|<span class="blue-text">EXAMPLE:</span> D, P
|
|<span class="blue-text">EXAMPLE:</span>
Common recurrent secondary finding for t(8;21) (add references).
|-
|<span class="blue-text">EXAMPLE:</span>
17
|<span class="blue-text">EXAMPLE:</span> Amp
|<span class="blue-text">EXAMPLE:</span>
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
 
''ERBB2''
chr8
|<span class="blue-text">EXAMPLE:</span> D, P, T
|No
|
|No
|No
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
 
Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.
Common recurrent secondary finding for t(8;21) (add reference).
|-
|
|
|
|
|
|
|
|}
|}
==Characteristic Chromosomal Patterns==
==Characteristic Chromosomal or Other Global Mutational Patterns==


Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis. Do not delete table.'')</span>


Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosomal Pattern
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Molecular Pathogenesis
!Prognostic Significance (Yes, No or Unknown)
!Prevalence -
!Therapeutic Significance (Yes, No or Unknown)
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Notes
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
Co-deletion of 1p and 18q
Co-deletion of 1p and 18q
|Yes
|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|No
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
|No
|<span class="blue-text">EXAMPLE:</span> D, P
|
|
|-
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
 
Microsatellite instability - hypermutated
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|
|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
|<span class="blue-text">EXAMPLE:</span> P, T
|
|
|-
|
|
|
|
|
|
|}
|}


<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}
<blockquote class="blockedit">{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}</blockquote>




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<br />
<br />


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Gene Mutations (SNV / INDEL)==
==Gene Mutations (SNV/INDEL)==


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well as either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable. Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Do not delete table.'') </span>


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
!'''Diagnostic Significance (Yes, No or Unknown)'''
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Prognostic Significance (Yes, No or Unknown)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  
!Therapeutic Significance (Yes, No or Unknown)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span> TP53; Variable LOF mutations
|<span class="blue-text">EXAMPLE:</span>''EGFR''


<span class="blue-text">EXAMPLE:</span>
<br />
 
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
EGFR; Exon 20 mutations
|<span class="blue-text">EXAMPLE:</span> Oncogene
 
|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
<span class="blue-text">EXAMPLE:</span> BRAF; Activating mutations
|<span class="blue-text">EXAMPLE:</span> T
|<span class="blue-text">EXAMPLE:</span> TSG
|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
|<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
|<span class="blue-text">EXAMPLE:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
 
|-
<span class="blue-text">EXAMPLE:</span> 30% (add Reference)
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
|<span class="blue-text">EXAMPLE:</span> IDH1 R123H
<br />
|<span class="blue-text">EXAMPLE:</span> EGFR amplification
|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
|<span class="blue-text">EXAMPLE:</span> P
|
|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
|-
|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
|<span class="blue-text">EXAMPLE:</span> Activating mutations
|<span class="blue-text">EXAMPLE:</span> Oncogene
|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
|<span class="blue-text">EXAMPLE:</span> T
|
|
|-
|
|
|
|
|
|
|
|
|
|
|<span class="blue-text">EXAMPLE:</span>  Excludes hairy cell leukemia (HCL) (add reference).
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
<br />
|}
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
 


<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}
<blockquote class="blockedit">{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}</blockquote>


'''THIS SECTION NEEDS REFERENCES.'''  
'''THIS SECTION NEEDS REFERENCES.'''  
Line 555: Line 531:
|}
|}


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Epigenomic Alterations==
==Epigenomic Alterations==
Line 562: Line 541:
==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table. Do not delete table.'')</span>
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|<span class="blue-text">EXAMPLE:</span> BRAF and MAP2K1; Activating mutations
|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
|-
|-
|<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
|-
|-
|<span class="blue-text">EXAMPLE:</span>  KMT2C and ARID1A; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span>  Histone modification, chromatin remodeling
|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
|<span class="blue-text">EXAMPLE:</span>  Abnormal gene expression program
|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
|-
|
|
|
|}
|}


<blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}
<blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote>


Due to the wide spectrum of chromosomal abnormalities and somatic mutations identified in plasma cell myeloma, it’s believed that the oncogenesis and development of plasma cell myeloma may also involve many pathways.  Please refer to review articles for more detailed information. <ref name=":9" /><ref name=":11">{{Cite journal|last=Manier|first=Salomon|last2=Salem|first2=Karma Z.|last3=Park|first3=Jihye|last4=Landau|first4=Dan A.|last5=Getz|first5=Gad|last6=Ghobrial|first6=Irene M.|date=02 2017|title=Genomic complexity of multiple myeloma and its clinical implications|url=https://pubmed.ncbi.nlm.nih.gov/27531699|journal=Nature Reviews. Clinical Oncology|volume=14|issue=2|pages=100–113|doi=10.1038/nrclinonc.2016.122|issn=1759-4782|pmid=27531699}}</ref>  
Due to the wide spectrum of chromosomal abnormalities and somatic mutations identified in plasma cell myeloma, it’s believed that the oncogenesis and development of plasma cell myeloma may also involve many pathways.  Please refer to review articles for more detailed information. <ref name=":9" /><ref name=":11">{{Cite journal|last=Manier|first=Salomon|last2=Salem|first2=Karma Z.|last3=Park|first3=Jihye|last4=Landau|first4=Dan A.|last5=Getz|first5=Gad|last6=Ghobrial|first6=Irene M.|date=02 2017|title=Genomic complexity of multiple myeloma and its clinical implications|url=https://pubmed.ncbi.nlm.nih.gov/27531699|journal=Nature Reviews. Clinical Oncology|volume=14|issue=2|pages=100–113|doi=10.1038/nrclinonc.2016.122|issn=1759-4782|pmid=27531699}}</ref>  
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'''MYC activation''': ''MYC'' rearrangement is found in 8% of the newly diagnosed myeloma patient in a Mayo Clinic study. It is associated with high disease burden and is an independent adverse prognostic factor. <ref>{{Cite journal|last=Abdallah|first=Nadine|last2=Baughn|first2=Linda B.|last3=Rajkumar|first3=S. Vincent|last4=Kapoor|first4=Prashant|last5=Gertz|first5=Morie A.|last6=Dispenzieri|first6=Angela|last7=Lacy|first7=Martha Q.|last8=Hayman|first8=Suzanne R.|last9=Buadi|first9=Francis K.|date=2020-12-15|title=Implications of MYC Rearrangements in Newly Diagnosed Multiple Myeloma|url=https://pubmed.ncbi.nlm.nih.gov/33008815|journal=Clinical Cancer Research: An Official Journal of the American Association for Cancer Research|volume=26|issue=24|pages=6581–6588|doi=10.1158/1078-0432.CCR-20-2283|issn=1557-3265|pmid=33008815}}</ref>  
'''MYC activation''': ''MYC'' rearrangement is found in 8% of the newly diagnosed myeloma patient in a Mayo Clinic study. It is associated with high disease burden and is an independent adverse prognostic factor. <ref>{{Cite journal|last=Abdallah|first=Nadine|last2=Baughn|first2=Linda B.|last3=Rajkumar|first3=S. Vincent|last4=Kapoor|first4=Prashant|last5=Gertz|first5=Morie A.|last6=Dispenzieri|first6=Angela|last7=Lacy|first7=Martha Q.|last8=Hayman|first8=Suzanne R.|last9=Buadi|first9=Francis K.|date=2020-12-15|title=Implications of MYC Rearrangements in Newly Diagnosed Multiple Myeloma|url=https://pubmed.ncbi.nlm.nih.gov/33008815|journal=Clinical Cancer Research: An Official Journal of the American Association for Cancer Research|volume=26|issue=24|pages=6581–6588|doi=10.1158/1078-0432.CCR-20-2283|issn=1557-3265|pmid=33008815}}</ref>  


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==
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==References==
==References==
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span> <references />


'''
<br />


==Notes==
==Notes==
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<nowiki>*</nowiki>''Citation of this Page'': “Plasma cell myeloma / multiple myeloma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Plasma_cell_myeloma_/_multiple_myeloma</nowiki>.
<nowiki>*</nowiki>''Citation of this Page'': “Plasma cell myeloma / multiple myeloma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Plasma_cell_myeloma_/_multiple_myeloma</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases P]]
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:Diseases P]]