BRST5:Adenoid cystic carcinoma: Difference between revisions - Compendium of Cancer Genome Aberrations

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[[BRST5:Table_of_Contents|Breast Tumours (WHO Classification, 5th ed.)]]

(''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/ HUGO-approved gene names and symbols] (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 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'' ''[[Author_Instructions]]'' ''and [[Frequently Asked Questions (FAQs)|FAQs]] as well as contact your [[Leadership|Associate Editor]] or [mailto:CCGA@cancergenomics.org Technical Support].)''

==Primary Author(s)*==

Jun Liao, PhD, Columbia University Irving Medical Center, NY, USA

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Katherine Geiersbach, MD, Mayo Clinic - Rochester, MN, USA

==WHO Classification of Disease==

~~(''Instructions: This table’s content from the WHO book will be autocompleted.'')~~

{| class="wikitable"

!Structure

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|-

|Book

|

|Breast Tumours (5th ed.)

|-

|Category

|

|Epithelial tumours of the breast

|-

|Family

|

|Rare and salivary gland-type tumours: Introduction

|-

|Type

|

|Adenoid cystic carcinoma

|-

|Subtype(s)

|

|N/A

|}

==WHO Essential and Desirable Genetic Diagnostic Criteria==

(''Instructions: The table will have the diagnostic criteria from the WHO book autocompleted; remove any non-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')

{| class="wikitable"

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<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home WHO Classification of Tumours].

==Related Terminology==

(''Instructions: The table will have the related terminology from the WHO autocompleted.)''

{| class="wikitable"

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==Gene Rearrangements==

Put your text here and fill in the table (''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.'')

{| class="wikitable sortable"

|-

!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

|-

|EXAMPLE: ''ABL1''||EXAMPLE: ''BCR::ABL1''||EXAMPLE: The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||EXAMPLE: t(9;22)(q34;q11.2)

|EXAMPLE: Common (CML)

|EXAMPLE: D, P, T

|EXAMPLE: Yes (WHO, NCCN)

|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). BCR::ABL1 is generally favorable in CML (add reference).

|-

|EXAMPLE: ''CIC''

|EXAMPLE: ''CIC::DUX4''

|EXAMPLE: 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''.

|EXAMPLE: t(4;19)(q25;q13)

|EXAMPLE: Common (CIC-rearranged sarcoma)

|EXAMPLE: D

|

|EXAMPLE:

''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).

|-

|EXAMPLE: ''ALK''

|EXAMPLE: ''ELM4::ALK''

Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''

|EXAMPLE: 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.

|EXAMPLE: N/A

|EXAMPLE: Rare (Lung adenocarcinoma)

|EXAMPLE: T

|

|EXAMPLE:

Both balanced and unbalanced forms are observed by FISH (add references).

|-

|EXAMPLE: ''ABL1''

|EXAMPLE: N/A

|EXAMPLE: 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.

|EXAMPLE: N/A

|EXAMPLE: Recurrent (IDH-wildtype Glioblastoma)

|EXAMPLE: D, P, T

|

|-

|

|}

{| class="wikitable sortable"

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|

|}

==Individual Region Genomic Gain/Loss/LOH==

Put your text here and fill in the table (''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.'')

{| class="wikitable sortable"

|-

!Chr #!!'''Gain, Loss, Amp, LOH'''!!'''Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]'''!!'''Relevant Gene(s)'''

!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''

!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''

!'''Clinical Relevance Details/Other Notes'''

|-

|EXAMPLE:

7

|EXAMPLE: Loss

|EXAMPLE:

chr7

|EXAMPLE:

Unknown

|EXAMPLE: D, P

|EXAMPLE: No

|EXAMPLE:

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:

8

|EXAMPLE: Gain

|EXAMPLE:

chr8

|EXAMPLE:

Unknown

|EXAMPLE: D, P

|

|EXAMPLE:

Common recurrent secondary finding for t(8;21) (add references).

|-

|EXAMPLE:

17

|EXAMPLE: Amp

|EXAMPLE:

17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]

|EXAMPLE:

''ERBB2''

|EXAMPLE: D, P, T

|

|EXAMPLE:

Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.

|-

|

|}

{| class="wikitable sortable"

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|

|}

==Characteristic Chromosomal or Other Global Mutational Patterns==

Put your text here and fill in the table (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.'')

{| class="wikitable sortable"

|-

!Chromosomal Pattern

!Molecular Pathogenesis

!'''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'''

|-

|EXAMPLE:

Co-deletion of 1p and 18q

|EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

|EXAMPLE: Common (Oligodendroglioma)

|EXAMPLE: D, P

|

|-

|EXAMPLE:

Microsatellite instability - hypermutated

|

|EXAMPLE: Common (Endometrial carcinoma)

|EXAMPLE: P, T

|

|-

|

|}

{| class="wikitable sortable"

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|

|}

==Gene Mutations (SNV/INDEL)==

Put your text here and fill in the table (''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.'')

{| class="wikitable sortable"

|-

!Gene!!'''Genetic Alteration'''!!'''Tumor Suppressor Gene, Oncogene, Other'''!!'''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'''

|-

|EXAMPLE:''EGFR''

|EXAMPLE: Exon 18-21 activating mutations

|EXAMPLE: Oncogene

|EXAMPLE: Common (lung cancer)

|EXAMPLE: T

|EXAMPLE: Yes (NCCN)

|EXAMPLE: 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: ''TP53''; Variable LOF mutations

|EXAMPLE: Variable LOF mutations

|EXAMPLE: Tumor Supressor Gene

|EXAMPLE: Common (breast cancer)

|EXAMPLE: P

|

|EXAMPLE: >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.

|-

|EXAMPLE: ''BRAF''; Activating mutations

|EXAMPLE: Activating mutations

|EXAMPLE: Oncogene

|EXAMPLE: Common (melanoma)

|EXAMPLE: T

|

|-

|

|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ cBioportal], [https://cancer.sanger.ac.uk/cosmic COSMIC], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

Recurrent mutations are shown in the table below. Adenoid cystic carcinoma does not share the typical mutation profile of most triple negative breast cancers and generally lacks mutations in ''TP53'', ''PIK3CA'', and ''BRCA1''.<ref name=":0" /> Progression to high-grade triple-negative breast cancer has been described, with additional sub-clonal mutations in genes including ''MYB''.<ref>{{Cite journal|last=Fusco|first=Nicola|last2=Geyer|first2=Felipe C.|last3=De Filippo|first3=Maria R.|last4=Martelotto|first4=Luciano G.|last5=Ng|first5=Charlotte K. Y.|last6=Piscuoglio|first6=Salvatore|last7=Guerini-Rocco|first7=Elena|last8=Schultheis|first8=Anne M.|last9=Fuhrmann|first9=Laetitia|date=2016-11|title=Genetic events in the progression of adenoid cystic carcinoma of the breast to high-grade triple-negative breast cancer|url=https://pubmed.ncbi.nlm.nih.gov/27491809|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=29|issue=11|pages=1292–1305|doi=10.1038/modpathol.2016.134|issn=1530-0285|pmc=5083185|pmid=27491809}}</ref>

{| class="wikitable sortable"

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|

|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ cBioportal], [https://cancer.sanger.ac.uk/cosmic COSMIC], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

==Epigenomic Alterations==

==Genes and Main Pathways Involved==

Put your text here and fill in the table (''Instructions: Please include references throughout the table. Do not delete the table.)''

{| class="wikitable sortable"

|-

!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome

|-

|EXAMPLE: ''BRAF'' and ''MAP2K1''; Activating mutations

|EXAMPLE: MAPK signaling

|EXAMPLE: Increased cell growth and proliferation

|-

|EXAMPLE: ''CDKN2A''; Inactivating mutations

|EXAMPLE: Cell cycle regulation

|EXAMPLE: Unregulated cell division

|-

|EXAMPLE: ''KMT2C'' and ''ARID1A''; Inactivating mutations

|EXAMPLE: Histone modification, chromatin remodeling

|EXAMPLE: Abnormal gene expression program

|-

|

|}

{| class="wikitable sortable"

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|

|}

==Genetic Diagnostic Testing Methods==

Next generation sequencing for fusion detection and gene mutation profiling as applicable. Fluorescence in situ hybridization (FISH) for ''MYB'' rearrangement, typically with a "break-apart" probe design using differentially labeled 5' and 3' flanking probes to detect rearrangements of the ''MYB'' gene locus. Immunohistochemistry for MYB expression was more sensitive and specific than FISH in one study<ref>{{Cite journal|last=Poling|first=Justin S.|last2=Yonescu|first2=Raluca|last3=Subhawong|first3=Andrea P.|last4=Sharma|first4=Rajni|last5=Argani|first5=Pedram|last6=Ning|first6=Yi|last7=Cimino-Mathews|first7=Ashley|date=2017-07|title=MYB Labeling by Immunohistochemistry Is More Sensitive and Specific for Breast Adenoid Cystic Carcinoma than MYB Labeling by FISH|url=https://pubmed.ncbi.nlm.nih.gov/28498281|journal=The American Journal of Surgical Pathology|volume=41|issue=7|pages=973–979|doi=10.1097/PAS.0000000000000878|issn=1532-0979|pmid=28498281}}</ref> but was demonstrated to be less specific with MYB staining also present in adenomyoepithelioma of the breast in another study.<ref>{{Cite journal|last=Baraban|first=Ezra|last2=Zhang|first2=Paul J.|last3=Jaffer|first3=Shabnam|last4=Lubin|first4=Daniel|last5=Feldman|first5=Michael|last6=Bleiweiss|first6=Ira J.|last7=Nayak|first7=Anupma|date=2018-12|title=MYB rearrangement and immunohistochemical expression in adenomyoepithelioma of the breast: a comparison with adenoid cystic carcinoma|url=https://pubmed.ncbi.nlm.nih.gov/30003572|journal=Histopathology|volume=73|issue=6|pages=897–903|doi=10.1111/his.13708|issn=1365-2559|pmid=30003572}}</ref>

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None

==Additional Information==

Put your text here

==Links==

https://www.pathologyoutlines.com/topic/breastmalignantadenoidcystic.html

==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 [[Leadership|''Associate Editor'']] 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):

==References==

(use the "Cite" icon at the top of the page) (''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''''.'')

<nowiki>*</nowiki>''Citation of this Page'': “Adenoid cystic carcinoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/BRST5:Adenoid cystic carcinoma</nowiki>.

[[Category:BRST5]][[Category:DISEASE]][[Category:Diseases A]]

@@ Line 1: / Line 1: @@
-<br />
+{{DISPLAYTITLE:Adenoid cystic carcinoma}}
+[[BRST5:Table_of_Contents|Breast Tumours (WHO Classification, 5th ed.)]]
+{{Under Construction}}
+<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)*==
 Jun Liao, PhD, Columbia University Irving Medical Center, NY, USA
@@ Line 5: / Line 10: @@
 Katherine Geiersbach, MD, Mayo Clinic - Rochester, MN, USA
 ==WHO Classification of Disease==
-<span style="color:#0070C0">(''Instructions: This table’s content from the WHO book will be <u>autocompleted</u>.'')</span>
 {| class="wikitable"
 !Structure
@@ Line 11: / Line 16: @@
 |-
 |Book
-|
+|Breast Tumours (5th ed.)
 |-
 |Category
-|
+|Epithelial tumours of the breast
 |-
 |Family
-|
+|Rare and salivary gland-type tumours: Introduction
 |-
 |Type
-|
+|Adenoid cystic carcinoma
 |-
 |Subtype(s)
-|
+|N/A
 |}
 ==WHO Essential and Desirable Genetic Diagnostic Criteria==
 <span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span>
 {| class="wikitable"
@@ Line 40: / Line 48: @@
 <nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
 ==Related Terminology==
 <span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>
 {| class="wikitable"
@@ Line 51: / Line 61: @@
 ==Gene Rearrangements==
+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"
+|-
+!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
+|-
+|<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).
+|-
+|<span class="blue-text">EXAMPLE:</span> ''CIC''
+|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
+|<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).
+|-
+|<span class="blue-text">EXAMPLE:</span> ''ALK''
+|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
+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.
+|<span class="blue-text">EXAMPLE:</span> N/A
+|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
+|<span class="blue-text">EXAMPLE:</span> T
+|
+|<span class="blue-text">EXAMPLE:</span>
+Both balanced and unbalanced forms are observed by FISH (add references).
+|-
+|<span class="blue-text">EXAMPLE:</span> ''ABL1''
+|<span class="blue-text">EXAMPLE:</span> N/A
+|<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.
+|<span class="blue-text">EXAMPLE:</span> N/A
+|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
+|<span class="blue-text">EXAMPLE:</span> D, P, T
+|
+|
+|-
+|
+|
+|
+|
+|
+|
+|
+|
+|}
 <br />
 {| class="wikitable sortable"
@@ Line 78: / Line 150: @@
 |
 |}
 ==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 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"
+|-
+!Chr #!!'''Gain, Loss, Amp, LOH'''!!'''Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]'''!!'''Relevant Gene(s)'''
+!'''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> Loss
+|<span class="blue-text">EXAMPLE:</span>
+chr7
+|<span class="blue-text">EXAMPLE:</span>
+Unknown
+|<span class="blue-text">EXAMPLE:</span> D, P
+|<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 references).
+|-
+|<span class="blue-text">EXAMPLE:</span>
+|<span class="blue-text">EXAMPLE:</span> Gain
+|<span class="blue-text">EXAMPLE:</span>
+chr8
+|<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>
+|<span class="blue-text">EXAMPLE:</span> Amp
+|<span class="blue-text">EXAMPLE:</span>
+q12; 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.
+|-
+|
+|
+|
+|
+|
+|
+|
+|}
 <br />
 {| class="wikitable sortable"
@@ Line 111: / Line 240: @@
 |
 |}
 ==Characteristic Chromosomal or Other Global Mutational Patterns==
+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"
+|-
+!Chromosomal Pattern
+!Molecular Pathogenesis
+!'''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'''
+|-
+|<span class="blue-text">EXAMPLE:</span>
+Co-deletion of 1p and 18q
+|<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).
+|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
+|<span class="blue-text">EXAMPLE:</span> D, P
+|
+|
+|-
+|<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
+|
+|
+|-
+|
+|
+|
+|
+|
+|
+|}
 <br />
 {| class="wikitable sortable"
@@ Line 130: / Line 298: @@
 |
 |}
 ==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 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"
+|-
+!Gene!!'''Genetic Alteration'''!!'''Tumor Suppressor Gene, Oncogene, Other'''!!'''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'''
+|-
+|<span class="blue-text">EXAMPLE:</span>''EGFR''
+<br />
+|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
+|<span class="blue-text">EXAMPLE:</span> Oncogene
+|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
+|<span class="blue-text">EXAMPLE:</span> T
+|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
+|<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> ''TP53''; Variable LOF mutations
+<br />
+|<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
+|
+|
+|-
+|
+|
+|
+|
+|
+|
+|
+|}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.
 Recurrent mutations are shown in the table below. Adenoid cystic carcinoma does not share the typical mutation profile of most triple negative breast cancers and generally lacks mutations in ''TP53'', ''PIK3CA'', and ''BRCA1''.<ref name=":0" /> Progression to high-grade triple-negative breast cancer has been described, with additional sub-clonal mutations in genes including ''MYB''.<ref>{{Cite journal|last=Fusco|first=Nicola|last2=Geyer|first2=Felipe C.|last3=De Filippo|first3=Maria R.|last4=Martelotto|first4=Luciano G.|last5=Ng|first5=Charlotte K. Y.|last6=Piscuoglio|first6=Salvatore|last7=Guerini-Rocco|first7=Elena|last8=Schultheis|first8=Anne M.|last9=Fuhrmann|first9=Laetitia|date=2016-11|title=Genetic events in the progression of adenoid cystic carcinoma of the breast to high-grade triple-negative breast cancer|url=https://pubmed.ncbi.nlm.nih.gov/27491809|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=29|issue=11|pages=1292–1305|doi=10.1038/modpathol.2016.134|issn=1530-0285|pmc=5083185|pmid=27491809}}</ref><br />
 {| class="wikitable sortable"
@@ Line 220: / Line 437: @@
 |
 |}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.
 ==Epigenomic Alterations==
 <br />
 ==Genes and Main Pathways Involved==
+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"
+|-
+!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
+|-
+|<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> Increased cell growth and proliferation
+|-
+|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
+|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
+|<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> Histone modification, chromatin remodeling
+|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
+|-
+|
+|
+|
+|}
 <br />
 {| class="wikitable sortable"
@@ Line 236: / Line 479: @@
 |
 |}
 ==Genetic Diagnostic Testing Methods==
 Next generation sequencing for fusion detection and gene mutation profiling as applicable. Fluorescence in situ hybridization (FISH) for ''MYB'' rearrangement, typically with a "break-apart" probe design using differentially labeled 5' and 3' flanking probes to detect rearrangements of the ''MYB'' gene locus. Immunohistochemistry for MYB expression was more sensitive and specific than FISH in one study<ref>{{Cite journal|last=Poling|first=Justin S.|last2=Yonescu|first2=Raluca|last3=Subhawong|first3=Andrea P.|last4=Sharma|first4=Rajni|last5=Argani|first5=Pedram|last6=Ning|first6=Yi|last7=Cimino-Mathews|first7=Ashley|date=2017-07|title=MYB Labeling by Immunohistochemistry Is More Sensitive and Specific for Breast Adenoid Cystic Carcinoma than MYB Labeling by FISH|url=https://pubmed.ncbi.nlm.nih.gov/28498281|journal=The American Journal of Surgical Pathology|volume=41|issue=7|pages=973–979|doi=10.1097/PAS.0000000000000878|issn=1532-0979|pmid=28498281}}</ref> but was demonstrated to be less specific with MYB staining also present in adenomyoepithelioma of the breast in another study.<ref>{{Cite journal|last=Baraban|first=Ezra|last2=Zhang|first2=Paul J.|last3=Jaffer|first3=Shabnam|last4=Lubin|first4=Daniel|last5=Feldman|first5=Michael|last6=Bleiweiss|first6=Ira J.|last7=Nayak|first7=Anupma|date=2018-12|title=MYB rearrangement and immunohistochemical expression in adenomyoepithelioma of the breast: a comparison with adenoid cystic carcinoma|url=https://pubmed.ncbi.nlm.nih.gov/30003572|journal=Histopathology|volume=73|issue=6|pages=897–903|doi=10.1111/his.13708|issn=1365-2559|pmid=30003572}}</ref>
@@ Line 241: / Line 486: @@
 None
 ==Additional Information==
 Put your text here
 ==Links==
 https://www.pathologyoutlines.com/topic/breastmalignantadenoidcystic.html
 ==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 [[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):
 <br />
 ==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 />
+<nowiki>*</nowiki>''Citation of this Page'': “Adenoid cystic carcinoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/BRST5:Adenoid cystic carcinoma</nowiki>.
+[[Category:BRST5]][[Category:DISEASE]][[Category:Diseases A]]