Compendium of Cancer Genome Aberrations

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{{DISPLAYTITLE:Blastic plasmacytoid dendritic cell neoplasm}}
{{DISPLAYTITLE:Blastic plasmacytoid dendritic cell neoplasm}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]


{{Under Construction}}
{{Under Construction}}


<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-11-30. The original page can be found at [[HAEM4:Blastic Plasmacytoid Dendritic Cell Neoplasm]].
<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:Blastic Plasmacytoid Dendritic Cell Neoplasm]].
}}</blockquote>
}}</blockquote>
<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)*==


Hao Liu, MD and Daynna J. Wolff, PhD
Hao Liu, MD and Daynna J. Wolff, PhD
==WHO Classification of Disease==


__TOC__
{| class="wikitable"
 
!Structure
==Cancer Category / Type==
!Disease
 
|-
Myeloid neoplasms/Acute myeloid leukemia
|Book
 
|Haematolymphoid Tumours (5th ed.)
==Cancer Sub-Classification / Subtype==
|-
 
|Category
Blastic plasmacytoid dendritic cell neoplasm (BPDCN)
|Histiocytic/Dendritic cell neoplasms
 
|-
==Definition / Description of Disease==
|Family
 
|Plasmacytoid dendritic cell neoplasms
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, clinically aggressive hematologic malignancy that derives from precursors of plasmacytoid dendritic cells (pDCs)<ref name=":0">Fachetti F, et al., (2017). Blastic plasmacytoid dendritic cell neoplasm, 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, p174-177.</ref><ref name=":1">{{Cite journal|last=Sapienza|first=Maria Rosaria|last2=Pileri|first2=Alessandro|last3=Derenzini|first3=Enrico|last4=Melle|first4=Federica|last5=Motta|first5=Giovanna|last6=Fiori|first6=Stefano|last7=Calleri|first7=Angelica|last8=Pimpinelli|first8=Nicola|last9=Tabanelli|first9=Valentina|date=2019|title=Blastic Plasmacytoid Dendritic Cell Neoplasm: State of the Art and Prospects|url=https://www.ncbi.nlm.nih.gov/pubmed/31035408|journal=Cancers|volume=11|issue=5|doi=10.3390/cancers11050595|issn=2072-6694|pmc=6562663|pmid=31035408}}</ref>.
|-
 
|Type
==Synonyms / Terminology==
|Plasmacytoid dendritic cell neoplasms
 
|-
* Agranular CD4+ NK cell leukaemia (obsolete)<ref name=":0" />
|Subtype(s)
* Blastic NK leukaemia/lymphoma (obsolete)<ref name=":0" />
|Blastic plasmacytoid dendritic cell neoplasm
* Agranular CD4+ CD56+ hematodermic neoplasm/tumor<ref name=":0" /><ref name=":1" />
|}
 
==Epidemiology / Prevalence==
 
*BPDCN is rare, estimated to represent < 1% of all hematologic malignancies<ref name=":0" />.
 
*The incidence of BPDCN in the USA: 0.04 cases per 100,000 individuals<ref name=":2">{{Cite journal|last=Khoury|first=Joseph D.|date=2018|title=Blastic Plasmacytoid Dendritic Cell Neoplasm|url=https://www.ncbi.nlm.nih.gov/pubmed/30350260|journal=Current Hematologic Malignancy Reports|volume=13|issue=6|pages=477–483|doi=10.1007/s11899-018-0489-z|issn=1558-822X|pmid=30350260}}</ref>.
 
*BPDCN has no known racial or ethnic predilection.
 
*Though BPDCN can occur at any age, it more commonly occurs in elderly patients with a mean/median patient age at diagnosis of 61-67 years<ref name=":0" /><ref name=":3">{{Cite journal|last=Kerr|first=Daniel|last2=Zhang|first2=Ling|last3=Sokol|first3=Lubomir|date=2019|title=Blastic Plasmacytoid Dendritic Cell Neoplasm|url=https://www.ncbi.nlm.nih.gov/pubmed/30715612|journal=Current Treatment Options in Oncology|volume=20|issue=1|pages=9|doi=10.1007/s11864-019-0605-x|issn=1534-6277|pmid=30715612}}</ref>.
 
*It most often affects males, with a male-to-female ratio of 3.3:1<ref name=":0" />.


==Clinical Features==
==Related Terminology==


Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
{| class="wikitable"
{| class="wikitable"
|'''Signs and Symptoms'''
|+
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
|Acceptable
 
|N/A
EXAMPLE B-symptoms (weight loss, fever, night sweats)
 
EXAMPLE Fatigue
 
EXAMPLE Lymphadenopathy (uncommon)
|-
|-
|'''Laboratory Findings'''
|Not Recommended
|EXAMPLE Cytopenias
|Blastic NK-cell lymphoma; agranular CD4+ NK-cell leukaemia; blastic NK-cell leukaemia/lymphoma; agranular CD4+ CD56+ haematodermic neoplasm/tumour
 
EXAMPLE 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.}}
Typical BPDCN patients may have two stages<ref name=":0" />:
o  First stage: affects the skin , usually contained or indolent
o  Second stage:  rapid leukemic spread and multi-organ involvement that eventually leads to death<ref name=":0" />.
</blockquote>
==Sites of Involvement==
*Multiple sites are frequently involved by BPDCN. The three most common are the skin (in 60–100% cases), followed by the bone-marrow and peripheral blood (in 60–90% of cases), and thirdly the lymph nodes (in 40–50% of cases)<ref name=":0" />.
*Upon diagnosis, the central nervous system (CNS) is also frequently found to be involved, and up to one third of patients have CNS involvement at relapse<ref name=":2" />.
==Morphologic Features==
*BPDCN is commonly characterized by a diffuse, monomorphous infiltrate of small or medium-sized blasts<ref name=":0" />.
*The morphology of the neoplastic cells is similar to lymphoblasts or myeloblasts:  high N: C ratio, eccentrically located nucleus, fine chromatin, a prominent nucleolus and scant amphophilic cytoplasm<ref name=":0" />.
*Mitoses are variable in number, and the Ki-67 rate ranges from 20 to 80%<ref name=":0" />.
*Necrosis may present.
==Immunophenotype==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the 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)||EXAMPLE 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)||EXAMPLE CD2
|<span class="blue-text">EXAMPLE:</span> ''CIC''
|-
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
|Negative (universal)||EXAMPLE 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)||EXAMPLE 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.
*BPDCN cells express CD4, CD43, CD45RA, CD56, and the pDC associated antigens, including CD123 (IL3 α chain receptor), CD303, TCL1A, CD2AP, and TCF4<ref name=":0" /><ref name=":1" /><ref name=":2" />.
|<span class="blue-text">EXAMPLE:</span> N/A
 
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
*BPDCN is characterized by high expression levels of CD123 and weak expression of CD45<ref name=":0" />.
|<span class="blue-text">EXAMPLE:</span> T
 
|
*BPDCN cells are negative for lineage-specific markers including CD3, CD19, and myeloperoxidase<ref name=":0" /><ref name=":2" />.
|<span class="blue-text">EXAMPLE:</span>
 
*BPDCN cells also do not express myeloid cell nuclear differentiation antigen (MNDA)<ref name=":2" />.
 
*BPDCN cells in some cases variably express CD2, CD5, CD7, CD33, CD38, CD68, CD117, HLA-DR, and TdT<ref name=":0" /><ref name=":2" />.
 
</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
|
|
|-
|-
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
|
EXAMPLE 30% (add reference)
|
|Yes
|
|No
|
|Yes
|
|EXAMPLE
|
 
|
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:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}
<blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>


A recurrent balanced translocation t(6;8)(p21;q24) involving the ''MYC'' locus was exclusively identified in BPDCN<ref name=":4">{{Cite journal|last=Kubota|first=Sho|last2=Tokunaga|first2=Kenji|last3=Umezu|first3=Tomohiro|last4=Yokomizo-Nakano|first4=Takako|last5=Sun|first5=Yuqi|last6=Oshima|first6=Motohiko|last7=Tan|first7=Kar Tong|last8=Yang|first8=Henry|last9=Kanai|first9=Akinori|date=2019|title=Lineage-specific RUNX2 super-enhancer activates MYC and promotes the development of blastic plasmacytoid dendritic cell neoplasm|url=https://www.ncbi.nlm.nih.gov/pubmed/30971697|journal=Nature Communications|volume=10|issue=1|pages=1653|doi=10.1038/s41467-019-09710-z|issn=2041-1723|pmc=6458132|pmid=30971697}}</ref><ref name=":5">{{Cite journal|last=Sumarriva Lezama|first=Lhara|last2=Chisholm|first2=Karen M.|last3=Carneal|first3=Eugene|last4=Nagy|first4=Alexandra|last5=Cascio|first5=Michael J.|last6=Yan|first6=Jie|last7=Chang|first7=Chung-Che|last8=Cherry|first8=Athena|last9=George|first9=Tracy I.|date=2018|title=An analysis of blastic plasmacytoid dendritic cell neoplasm with translocations involving the MYC locus identifies t(6;8)(p21;q24) as a recurrent cytogenetic abnormality|url=https://www.ncbi.nlm.nih.gov/pubmed/29884995|journal=Histopathology|volume=73|issue=5|pages=767–776|doi=10.1111/his.13668|issn=1365-2559|pmid=29884995}}</ref><ref name=":6">{{Cite journal|last=Nakamura|first=Y.|last2=Kayano|first2=H.|last3=Kakegawa|first3=E.|last4=Miyazaki|first4=H.|last5=Nagai|first5=T.|last6=Uchida|first6=Y.|last7=Ito|first7=Y.|last8=Wakimoto|first8=N.|last9=Mori|first9=S.|date=2015|title=Identification of SUPT3H as a novel 8q24/MYC partner in blastic plasmacytoid dendritic cell neoplasm with t(6;8)(p21;q24) translocation|url=https://www.ncbi.nlm.nih.gov/pubmed/25860292|journal=Blood Cancer Journal|volume=5|pages=e301|doi=10.1038/bcj.2015.26|issn=2044-5385|pmc=4450326|pmid=25860292}}</ref><ref name=":7">{{Cite journal|last=Sakamoto|first=Kana|last2=Katayama|first2=Ryohei|last3=Asaka|first3=Reimi|last4=Sakata|first4=Seiji|last5=Baba|first5=Satoko|last6=Nakasone|first6=Hideki|last7=Koike|first7=Sumie|last8=Tsuyama|first8=Naoko|last9=Dobashi|first9=Akito|date=2018|title=Recurrent 8q24 rearrangement in blastic plasmacytoid dendritic cell neoplasm: association with immunoblastoid cytomorphology, MYC expression, and drug response|url=https://www.ncbi.nlm.nih.gov/pubmed/29795241|journal=Leukemia|volume=32|issue=12|pages=2590–2603|doi=10.1038/s41375-018-0154-5|issn=1476-5551|pmid=29795241}}</ref><ref name=":8">{{Cite journal|last=Boddu|first=Prajwal C.|last2=Wang|first2=Sa A.|last3=Pemmaraju|first3=Naveen|last4=Tang|first4=Zhenya|last5=Hu|first5=Shimin|last6=Li|first6=Shaoying|last7=Xu|first7=Jie|last8=Medeiros|first8=L. Jeffrey|last9=Tang|first9=Guilin|date=2018|title=8q24/MYC rearrangement is a recurrent cytogenetic abnormality in blastic plasmacytoid dendritic cell neoplasms|url=https://www.ncbi.nlm.nih.gov/pubmed/29407586|journal=Leukemia Research|volume=66|pages=73–78|doi=10.1016/j.leukres.2018.01.013|issn=1873-5835|pmid=29407586}}</ref>. The prevalence of ''MYC'' translocation in BPDCN is 5% -12%<ref name=":5" />. Rearrangements involving the ''MYC'' locus on 8q24 are associated with MYC protein overexpression and specific clinical features, including older onset age and shorter median survival<ref name=":5" />. ''RUNX2'', located on chromosome 6p21, is strongly expressed in pDCs and BPDCN cells. The t(6,8) generates mutant-allele super-enhancer of ''RUNX2'' which may increase the expression of MYC and lead to the development of BPDCN<ref name=":4" />. SUPT3H, a TATA-binding protein-associated factors (TAF)-associated protein, was identified as a novel 8q24/''MYC'' partner in BPDCN<ref name=":6" />.
A recurrent balanced translocation t(6;8)(p21;q24) involving the ''MYC'' locus was exclusively identified in BPDCN<ref name=":4">{{Cite journal|last=Kubota|first=Sho|last2=Tokunaga|first2=Kenji|last3=Umezu|first3=Tomohiro|last4=Yokomizo-Nakano|first4=Takako|last5=Sun|first5=Yuqi|last6=Oshima|first6=Motohiko|last7=Tan|first7=Kar Tong|last8=Yang|first8=Henry|last9=Kanai|first9=Akinori|date=2019|title=Lineage-specific RUNX2 super-enhancer activates MYC and promotes the development of blastic plasmacytoid dendritic cell neoplasm|url=https://www.ncbi.nlm.nih.gov/pubmed/30971697|journal=Nature Communications|volume=10|issue=1|pages=1653|doi=10.1038/s41467-019-09710-z|issn=2041-1723|pmc=6458132|pmid=30971697}}</ref><ref name=":5">{{Cite journal|last=Sumarriva Lezama|first=Lhara|last2=Chisholm|first2=Karen M.|last3=Carneal|first3=Eugene|last4=Nagy|first4=Alexandra|last5=Cascio|first5=Michael J.|last6=Yan|first6=Jie|last7=Chang|first7=Chung-Che|last8=Cherry|first8=Athena|last9=George|first9=Tracy I.|date=2018|title=An analysis of blastic plasmacytoid dendritic cell neoplasm with translocations involving the MYC locus identifies t(6;8)(p21;q24) as a recurrent cytogenetic abnormality|url=https://www.ncbi.nlm.nih.gov/pubmed/29884995|journal=Histopathology|volume=73|issue=5|pages=767–776|doi=10.1111/his.13668|issn=1365-2559|pmid=29884995}}</ref><ref name=":6">{{Cite journal|last=Nakamura|first=Y.|last2=Kayano|first2=H.|last3=Kakegawa|first3=E.|last4=Miyazaki|first4=H.|last5=Nagai|first5=T.|last6=Uchida|first6=Y.|last7=Ito|first7=Y.|last8=Wakimoto|first8=N.|last9=Mori|first9=S.|date=2015|title=Identification of SUPT3H as a novel 8q24/MYC partner in blastic plasmacytoid dendritic cell neoplasm with t(6;8)(p21;q24) translocation|url=https://www.ncbi.nlm.nih.gov/pubmed/25860292|journal=Blood Cancer Journal|volume=5|pages=e301|doi=10.1038/bcj.2015.26|issn=2044-5385|pmc=4450326|pmid=25860292}}</ref><ref name=":7">{{Cite journal|last=Sakamoto|first=Kana|last2=Katayama|first2=Ryohei|last3=Asaka|first3=Reimi|last4=Sakata|first4=Seiji|last5=Baba|first5=Satoko|last6=Nakasone|first6=Hideki|last7=Koike|first7=Sumie|last8=Tsuyama|first8=Naoko|last9=Dobashi|first9=Akito|date=2018|title=Recurrent 8q24 rearrangement in blastic plasmacytoid dendritic cell neoplasm: association with immunoblastoid cytomorphology, MYC expression, and drug response|url=https://www.ncbi.nlm.nih.gov/pubmed/29795241|journal=Leukemia|volume=32|issue=12|pages=2590–2603|doi=10.1038/s41375-018-0154-5|issn=1476-5551|pmid=29795241}}</ref><ref name=":8">{{Cite journal|last=Boddu|first=Prajwal C.|last2=Wang|first2=Sa A.|last3=Pemmaraju|first3=Naveen|last4=Tang|first4=Zhenya|last5=Hu|first5=Shimin|last6=Li|first6=Shaoying|last7=Xu|first7=Jie|last8=Medeiros|first8=L. Jeffrey|last9=Tang|first9=Guilin|date=2018|title=8q24/MYC rearrangement is a recurrent cytogenetic abnormality in blastic plasmacytoid dendritic cell neoplasms|url=https://www.ncbi.nlm.nih.gov/pubmed/29407586|journal=Leukemia Research|volume=66|pages=73–78|doi=10.1016/j.leukres.2018.01.013|issn=1873-5835|pmid=29407586}}</ref>. The prevalence of ''MYC'' translocation in BPDCN is 5% -12%<ref name=":5" />. Rearrangements involving the ''MYC'' locus on 8q24 are associated with MYC protein overexpression and specific clinical features, including older onset age and shorter median survival<ref name=":5" />. ''RUNX2'', located on chromosome 6p21, is strongly expressed in pDCs and BPDCN cells. The t(6,8) generates mutant-allele super-enhancer of ''RUNX2'' which may increase the expression of MYC and lead to the development of BPDCN<ref name=":4" />. SUPT3H, a TATA-binding protein-associated factors (TAF)-associated protein, was identified as a novel 8q24/''MYC'' partner in BPDCN<ref name=":6" />.
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<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>




<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>


*BPDCN is extremely aggressive, with a median survival of 10-19.8 months<ref name=":0" />.
*BPDCN is extremely aggressive, with a median survival of 10-19.8 months<ref name=":0">Fachetti F, et al., (2017). Blastic plasmacytoid dendritic cell neoplasm, 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, p174-177.</ref>.


*Age is an adverse impact factor for prognosis<ref name=":0" />.
*Age is an adverse impact factor for prognosis<ref name=":0" />.


*Diagnosis is usually established through skin biopsy with immunohistochemistry or flow cytometry<ref name=":3" />.
*Diagnosis is usually established through skin biopsy with immunohistochemistry or flow cytometry<ref name=":3">{{Cite journal|last=Kerr|first=Daniel|last2=Zhang|first2=Ling|last3=Sokol|first3=Lubomir|date=2019|title=Blastic Plasmacytoid Dendritic Cell Neoplasm|url=https://www.ncbi.nlm.nih.gov/pubmed/30715612|journal=Current Treatment Options in Oncology|volume=20|issue=1|pages=9|doi=10.1007/s11864-019-0605-x|issn=1534-6277|pmid=30715612}}</ref>.


*Traditional therapeutic approaches include multi-agent chemotherapy, such as CHOP, hyper-CVAD<ref name=":1" /><ref name=":2" /><ref name=":3" />. However, the traditional chemotherapy is associated with high relapse rate and death<ref name=":12">{{Cite journal|last=Pemmaraju|first=Naveen|last2=Lane|first2=Andrew A.|last3=Sweet|first3=Kendra L.|last4=Stein|first4=Anthony S.|last5=Vasu|first5=Sumithira|last6=Blum|first6=William|last7=Rizzieri|first7=David A.|last8=Wang|first8=Eunice S.|last9=Duvic|first9=Madeleine|date=2019|title=Tagraxofusp in Blastic Plasmacytoid Dendritic-Cell Neoplasm|url=https://www.ncbi.nlm.nih.gov/pubmed/31018069|journal=The New England Journal of Medicine|volume=380|issue=17|pages=1628–1637|doi=10.1056/NEJMoa1815105|issn=1533-4406|pmid=31018069}}</ref>.
*Traditional therapeutic approaches include multi-agent chemotherapy, such as CHOP, hyper-CVAD<ref name=":1">{{Cite journal|last=Sapienza|first=Maria Rosaria|last2=Pileri|first2=Alessandro|last3=Derenzini|first3=Enrico|last4=Melle|first4=Federica|last5=Motta|first5=Giovanna|last6=Fiori|first6=Stefano|last7=Calleri|first7=Angelica|last8=Pimpinelli|first8=Nicola|last9=Tabanelli|first9=Valentina|date=2019|title=Blastic Plasmacytoid Dendritic Cell Neoplasm: State of the Art and Prospects|url=https://www.ncbi.nlm.nih.gov/pubmed/31035408|journal=Cancers|volume=11|issue=5|doi=10.3390/cancers11050595|issn=2072-6694|pmc=6562663|pmid=31035408}}</ref><ref name=":2">{{Cite journal|last=Khoury|first=Joseph D.|date=2018|title=Blastic Plasmacytoid Dendritic Cell Neoplasm|url=https://www.ncbi.nlm.nih.gov/pubmed/30350260|journal=Current Hematologic Malignancy Reports|volume=13|issue=6|pages=477–483|doi=10.1007/s11899-018-0489-z|issn=1558-822X|pmid=30350260}}</ref><ref name=":3" />. However, the traditional chemotherapy is associated with high relapse rate and death<ref name=":12">{{Cite journal|last=Pemmaraju|first=Naveen|last2=Lane|first2=Andrew A.|last3=Sweet|first3=Kendra L.|last4=Stein|first4=Anthony S.|last5=Vasu|first5=Sumithira|last6=Blum|first6=William|last7=Rizzieri|first7=David A.|last8=Wang|first8=Eunice S.|last9=Duvic|first9=Madeleine|date=2019|title=Tagraxofusp in Blastic Plasmacytoid Dendritic-Cell Neoplasm|url=https://www.ncbi.nlm.nih.gov/pubmed/31018069|journal=The New England Journal of Medicine|volume=380|issue=17|pages=1628–1637|doi=10.1056/NEJMoa1815105|issn=1533-4406|pmid=31018069}}</ref>.


*A new targeted therapy, Tagraxofusp (SL-401, ELZONRIS) was recently approved.  This agent is a CD123-directed cytotoxin consisting of recombinant human interleukin-3 fused to a truncated diphtheria toxin<ref name=":1" /><ref name=":3" /><ref name=":12" />.
*A new targeted therapy, Tagraxofusp (SL-401, ELZONRIS) was recently approved.  This agent is a CD123-directed cytotoxin consisting of recombinant human interleukin-3 fused to a truncated diphtheria toxin<ref name=":1" /><ref name=":3" /><ref name=":12" />.
Line 183: Line 153:
*For the patients in first complete remission after induction therapy, allogeneic hematopoietic stem cell transplantation (HSCT) is recommended to achieve long-term survival<ref name=":0" /><ref name=":3" />.
*For the patients in first complete remission after induction therapy, allogeneic hematopoietic stem cell transplantation (HSCT) is recommended to achieve long-term survival<ref name=":0" /><ref name=":3" />.


<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.'') </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
|-
|-
|EXAMPLE
|<span class="blue-text">EXAMPLE:</span>
 
7
7
|EXAMPLE Loss
|<span class="blue-text">EXAMPLE:</span> Loss
|EXAMPLE
|<span class="blue-text">EXAMPLE:</span>
 
chr7:1- 159,335,973 [hg38]
|EXAMPLE
 
chr7
chr7
|Yes
|<span class="blue-text">EXAMPLE:</span>
|Yes
Unknown
|No
|<span class="blue-text">EXAMPLE:</span> D, P
|EXAMPLE
|<span class="blue-text">EXAMPLE:</span> No
 
|<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 reference).
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).
|-
|-
|EXAMPLE
|<span class="blue-text">EXAMPLE:</span>
 
8
8
|EXAMPLE Gain
|<span class="blue-text">EXAMPLE:</span> Gain
|EXAMPLE
|<span class="blue-text">EXAMPLE:</span>
 
chr8:1-145,138,636 [hg38]
|EXAMPLE
 
chr8
chr8
|No
|<span class="blue-text">EXAMPLE:</span>
|No
Unknown
|No
|<span class="blue-text">EXAMPLE:</span> D, P
|EXAMPLE
|
 
|<span class="blue-text">EXAMPLE:</span>
Common recurrent secondary finding for t(8;21) (add reference).
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>
''ERBB2''
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|<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.
|-
|
|
|
|
|
|
|
|}
|}


<blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}
<blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote>


1).Deletion of the 9p21.3 locus<ref name=":10">{{Cite journal|last=Lezama|first=Lhara|last2=Ohgami|first2=Robert S.|date=2019|title=Expounding on the essence of epigenetic and genetic abnormalities in blastic plasmacytoid dendritic cell neoplasms|url=https://www.ncbi.nlm.nih.gov/pubmed/30930334|journal=Haematologica|volume=104|issue=4|pages=642–643|doi=10.3324/haematol.2018.211557|issn=1592-8721|pmc=6442968|pmid=30930334}}</ref>:
1).Deletion of the 9p21.3 locus<ref name=":10">{{Cite journal|last=Lezama|first=Lhara|last2=Ohgami|first2=Robert S.|date=2019|title=Expounding on the essence of epigenetic and genetic abnormalities in blastic plasmacytoid dendritic cell neoplasms|url=https://www.ncbi.nlm.nih.gov/pubmed/30930334|journal=Haematologica|volume=104|issue=4|pages=642–643|doi=10.3324/haematol.2018.211557|issn=1592-8721|pmc=6442968|pmid=30930334}}</ref>:
Line 247: Line 229:
3). Del(5q), del(7q), del(9q), del(11q), del(12p) and del(13q) are frequently identified in BPDCN patients with myelodysplastic syndrome or acute myeloid leukemia with myelodysplasia-related changes<ref name=":2" />.
3). Del(5q), del(7q), del(9q), del(11q), del(12p) and del(13q) are frequently identified in BPDCN patients with myelodysplastic syndrome or acute myeloid leukemia with myelodysplasia-related changes<ref name=":2" />.


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==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'')</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
|-
|-
|EXAMPLE
|<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
|EXAMPLE:
|
 
|
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>
Microsatellite instability - hypermutated
|
|<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>


*Chromosomal abnormalities are identified in the majority of BPDCN cases; about two thirds of BPDCN patients have an abnormal karyotype<ref name=":0" />.
*Chromosomal abnormalities are identified in the majority of BPDCN cases; about two thirds of BPDCN patients have an abnormal karyotype<ref name=":0" />.
Line 282: Line 282:
*Six major recurrent chromosomal targets were defined in one study<ref name=":9" />. These were 5q, 12p, 13q, 6q, 15q, and 9, which were involved in 72% (5q), 64% (12p and 13q), 50% (6q), 43% (15q), and 28% (monosomy 9) of cases, respectively.
*Six major recurrent chromosomal targets were defined in one study<ref name=":9" />. These were 5q, 12p, 13q, 6q, 15q, and 9, which were involved in 72% (5q), 64% (12p and 13q), 50% (6q), 43% (15q), and 28% (monosomy 9) of cases, respectively.


<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 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.'') </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
|-
|-
|EXAMPLE: TP53; Variable LOF mutations
|<span class="blue-text">EXAMPLE:</span>''EGFR''


EXAMPLE:
<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)
EXAMPLE: BRAF; Activating mutations
|<span class="blue-text">EXAMPLE:</span> T
|EXAMPLE: TSG
|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
|EXAMPLE: 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).
 
|-
EXAMPLE: 30% (add Reference)
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
|EXAMPLE: IDH1 R123H
<br />
|EXAMPLE: 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
|
|
|-
|
|
|
|
|
|
|
|
|
|
|EXAMPLE:  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>


*Common gene mutations in BPDCN: ''TET2'', ''ASXL1, NRAS, ATM'', and ''NPM1''<ref name=":0" /><ref name=":2" /><ref name=":5" /><ref name=":11">{{Cite journal|last=Sapienza|first=Maria Rosaria|last2=Abate|first2=Francesco|last3=Melle|first3=Federica|last4=Orecchioni|first4=Stefania|last5=Fuligni|first5=Fabio|last6=Etebari|first6=Maryam|last7=Tabanelli|first7=Valentina|last8=Laginestra|first8=Maria Antonella|last9=Pileri|first9=Alessandro|date=2019|title=Blastic plasmacytoid dendritic cell neoplasm: genomics mark epigenetic dysregulation as a primary therapeutic target|url=https://www.ncbi.nlm.nih.gov/pubmed/30381297|journal=Haematologica|volume=104|issue=4|pages=729–737|doi=10.3324/haematol.2018.202093|issn=1592-8721|pmc=6442957|pmid=30381297}}</ref>.
*Common gene mutations in BPDCN: ''TET2'', ''ASXL1, NRAS, ATM'', and ''NPM1''<ref name=":0" /><ref name=":2" /><ref name=":5" /><ref name=":11">{{Cite journal|last=Sapienza|first=Maria Rosaria|last2=Abate|first2=Francesco|last3=Melle|first3=Federica|last4=Orecchioni|first4=Stefania|last5=Fuligni|first5=Fabio|last6=Etebari|first6=Maryam|last7=Tabanelli|first7=Valentina|last8=Laginestra|first8=Maria Antonella|last9=Pileri|first9=Alessandro|date=2019|title=Blastic plasmacytoid dendritic cell neoplasm: genomics mark epigenetic dysregulation as a primary therapeutic target|url=https://www.ncbi.nlm.nih.gov/pubmed/30381297|journal=Haematologica|volume=104|issue=4|pages=729–737|doi=10.3324/haematol.2018.202093|issn=1592-8721|pmc=6442957|pmid=30381297}}</ref>.
Line 324: Line 341:


===Other Mutations===
===Other Mutations===
<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Epigenomic Alterations==
==Epigenomic Alterations==
Line 337: Line 357:
==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.'')</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
|-
|-
|EXAMPLE: BRAF and MAP2K1; Activating mutations
|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
|EXAMPLE: MAPK signaling
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|EXAMPLE: Increased cell growth and proliferation
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
|-
|-
|EXAMPLE: CDKN2A; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
|EXAMPLE: Cell cycle regulation
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|EXAMPLE: Unregulated cell division
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
|-
|-
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
|EXAMPLE:  Histone modification, chromatin remodeling
|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
|EXAMPLE:  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>


·        BCL-2 and NF-ĸB pathways<ref name=":10" /><ref>{{Cite journal|last=Chang|first=Kung-Chao|last2=Yu-Yun Lee|first2=Julia|last3=Sakamoto|first3=Kana|last4=Baba|first4=Satoko|last5=Takeuchi|first5=Kengo|date=2019|title=Blastic plasmacytoid dendritic cell neoplasm with immunoblastoid morphology and MYC rearrangement and overexpression|url=https://www.ncbi.nlm.nih.gov/pubmed/30482401|journal=Pathology|volume=51|issue=1|pages=100–102|doi=10.1016/j.pathol.2018.09.058|issn=1465-3931|pmid=30482401}}</ref>
·        BCL-2 and NF-ĸB pathways<ref name=":10" /><ref>{{Cite journal|last=Chang|first=Kung-Chao|last2=Yu-Yun Lee|first2=Julia|last3=Sakamoto|first3=Kana|last4=Baba|first4=Satoko|last5=Takeuchi|first5=Kengo|date=2019|title=Blastic plasmacytoid dendritic cell neoplasm with immunoblastoid morphology and MYC rearrangement and overexpression|url=https://www.ncbi.nlm.nih.gov/pubmed/30482401|journal=Pathology|volume=51|issue=1|pages=100–102|doi=10.1016/j.pathol.2018.09.058|issn=1465-3931|pmid=30482401}}</ref>


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==
Line 375: Line 403:


==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==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
 
Prior Author(s): 
 
       
<nowiki>*</nowiki>''Citation of this Page'': “Blastic plasmacytoid dendritic cell neoplasm”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Blastic_plasmacytoid_dendritic_cell_neoplasm</nowiki>.
<nowiki>*</nowiki>''Citation of this Page'': “Blastic plasmacytoid dendritic cell neoplasm”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Blastic_plasmacytoid_dendritic_cell_neoplasm</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases B]]
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:Diseases B]]
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