Adenoid cystic carcinoma

From Compendium of Cancer Genome Aberrations
Jump to navigation Jump to search

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 HUGO-approved gene names and symbols (italicized when appropriate), 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 FAQs as well as contact your Associate Editor or Technical Support.)

Primary Author(s)*

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

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

WHO Classification of Disease

Structure Disease
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.)

WHO Essential Criteria (Genetics)*
WHO Desirable Criteria (Genetics)*
Other Classification

*Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the WHO Classification of Tumours.

Related Terminology

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

Acceptable
Not Recommended

Gene Rearrangements


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
MYB MYB::NFIB Fusion transcripts most commonly join exon 8 or exon 14 of MYB with exon 9 of NFIB and result in overexpression of MYB.[1][2][3][4] Fusions translocate super-enhancers in the partner gene to MYB.[5] Fusion transcripts lack MYB exon 15 including the 3' UTR, which contains target sites for microRNAs that negatively regulate MYB.[1] t(6;9)(q23.3;p23) Common D Yes (WHO) Some breast cancers express more than one MYB::NFIB transcript or splice variant[2][3]
MYBL1 MYBL1::NFIB Fusions most commonly join exon 8 or exon 14 of MYBL1 with exon 11 of NFIB.[4] t(8;9)(q13.1;p23) Rare D Yes (WHO)


Individual Region Genomic Gain/Loss/LOH


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
6 Amp 6q23.3[6] MYB D Yes (WHO) Documented molecular pathogenesis in rare case lacking translocations of MYB or MYBL1[6]
12 Loss 12q12-q14.1[7] Unknown None No
17 Gain 17q21-q25.1[7] Unknown None No


Characteristic Chromosomal or Other Global Mutational Patterns


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


Gene Mutations (SNV/INDEL)

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.[7] Progression to high-grade triple-negative breast cancer has been described, with additional sub-clonal mutations in genes including MYB.[8]

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
MYB Activating mutations Oncogene Recurrent[7]
BRAF Activating mutations Oncogene Recurrent[9]
NOTCH1 Activating mutations Oncogene Rare[10][11] Enriched in solid-type adenoid cystic carcinomas of the breast[10][11]
KMT2C Activating mutations Oncogene Rare[11] Enriched in solid-type adenoid cystic carcinomas of the breast[11]
CREBBP Activating mutations Oncogene Rare[10][11] Enriched in solid-type adenoid cystic carcinomas of the breast[10][11]
FBXW7 Inactivating mutations Tumor Suppressor Gene Rare[7]
SMARCA5 Inactivating mutations Tumor Suppressor Gene Rare[7]
SF3B1 Activating mutations Other Rare[7]
FGFR2 Activating mutations Oncogene Rare[7]
MTOR Activating mutations Oncogene Rare[7]

Note: A more extensive list of mutations can be found in cBioportal, 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


Gene; Genetic Alteration Pathway Pathophysiologic Outcome
MYB or MYBL1; activating fusions most common; rarely other sequence or structural alterations or amplification Transcription factor Increased cell growth and proliferation[12]


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[13] but was demonstrated to be less specific with MYB staining also present in adenomyoepithelioma of the breast in another study.[14]

Familial Forms

None

Additional Information

Put your text here

Links

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

Notes

*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 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.)

  1. Jump up to: 1.0 1.1 Persson, Marta; et al. (2009-11-03). "Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck". Proceedings of the National Academy of Sciences of the United States of America. 106 (44): 18740–18744. doi:10.1073/pnas.0909114106. ISSN 1091-6490. PMC 2773970. PMID 19841262.
  2. Jump up to: 2.0 2.1 Brill, Louis B.; et al. (2011-09). "Analysis of MYB expression and MYB-NFIB gene fusions in adenoid cystic carcinoma and other salivary neoplasms". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 24 (9): 1169–1176. doi:10.1038/modpathol.2011.86. ISSN 1530-0285. PMID 21572406. Check date values in: |date= (help)
  3. Jump up to: 3.0 3.1 D'Alfonso, Timothy M.; et al. (2014-11). "MYB-NFIB gene fusion in adenoid cystic carcinoma of the breast with special focus paid to the solid variant with basaloid features". Human Pathology. 45 (11): 2270–2280. doi:10.1016/j.humpath.2014.07.013. ISSN 1532-8392. PMID 25217885. Check date values in: |date= (help)
  4. Jump up to: 4.0 4.1 Mitani, Yoshitsugu; et al. (2016-02-01). "Novel MYBL1 Gene Rearrangements with Recurrent MYBL1-NFIB Fusions in Salivary Adenoid Cystic Carcinomas Lacking t(6;9) Translocations". Clinical Cancer Research: An Official Journal of the American Association for Cancer Research. 22 (3): 725–733. doi:10.1158/1078-0432.CCR-15-2867-T. ISSN 1557-3265. PMC 4807116. PMID 26631609.
  5. Drier, Yotam; et al. (2016-03). "An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma". Nature Genetics. 48 (3): 265–272. doi:10.1038/ng.3502. ISSN 1546-1718. PMC 4767593. PMID 26829750. Check date values in: |date= (help)
  6. Jump up to: 6.0 6.1 Kim, Jisun; et al. (2018-02). "MYBL1 rearrangements and MYB amplification in breast adenoid cystic carcinomas lacking the MYB-NFIB fusion gene". The Journal of Pathology. 244 (2): 143–150. doi:10.1002/path.5006. ISSN 1096-9896. PMC 5839480. PMID 29149504. Check date values in: |date= (help)
  7. Jump up to: 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 Martelotto, Luciano G.; et al. (2015-10). "Genomic landscape of adenoid cystic carcinoma of the breast". The Journal of Pathology. 237 (2): 179–189. doi:10.1002/path.4573. ISSN 1096-9896. PMC 4676955. PMID 26095796. Check date values in: |date= (help)
  8. Fusco, Nicola; et al. (2016-11). "Genetic events in the progression of adenoid cystic carcinoma of the breast to high-grade triple-negative breast cancer". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 29 (11): 1292–1305. doi:10.1038/modpathol.2016.134. ISSN 1530-0285. PMC 5083185. PMID 27491809. Check date values in: |date= (help)
  9. Wetterskog, Daniel; et al. (2013-03). "Mutation profiling of adenoid cystic carcinomas from multiple anatomical sites identifies mutations in the RAS pathway, but no KIT mutations". Histopathology. 62 (4): 543–550. doi:10.1111/his.12050. ISSN 1365-2559. PMC 4975515. PMID 23398044. Check date values in: |date= (help)
  10. Jump up to: 10.0 10.1 10.2 10.3 Massé, Julie; et al. (2020-06). "Solid-type adenoid cystic carcinoma of the breast, a distinct molecular entity enriched in NOTCH and CREBBP mutations". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 33 (6): 1041–1055. doi:10.1038/s41379-019-0425-3. ISSN 1530-0285. PMID 31857685. Check date values in: |date= (help)
  11. Jump up to: 11.0 11.1 11.2 11.3 11.4 11.5 Schwartz, Christopher J.; et al. (2022-02). "The clinical behavior and genomic features of the so-called adenoid cystic carcinomas of the solid variant with basaloid features". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 35 (2): 193–201. doi:10.1038/s41379-021-00931-6. ISSN 1530-0285. PMC 9197148 Check |pmc= value (help). PMID 34599282 Check |pmid= value (help). Check date values in: |date= (help)
  12. Andersson, Mattias K.; et al. (2020-01-30). "ATR is a MYB regulated gene and potential therapeutic target in adenoid cystic carcinoma". Oncogenesis. 9 (1): 5. doi:10.1038/s41389-020-0194-3. ISSN 2157-9024. PMC 6992744. PMID 32001675 Check |pmid= value (help).
  13. Poling, Justin S.; et al. (2017-07). "MYB Labeling by Immunohistochemistry Is More Sensitive and Specific for Breast Adenoid Cystic Carcinoma than MYB Labeling by FISH". The American Journal of Surgical Pathology. 41 (7): 973–979. doi:10.1097/PAS.0000000000000878. ISSN 1532-0979. PMID 28498281. Check date values in: |date= (help)
  14. Baraban, Ezra; et al. (2018-12). "MYB rearrangement and immunohistochemical expression in adenomyoepithelioma of the breast: a comparison with adenoid cystic carcinoma". Histopathology. 73 (6): 897–903. doi:10.1111/his.13708. ISSN 1365-2559. PMID 30003572. Check date values in: |date= (help)

*Citation of this Page: “Adenoid cystic carcinoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 03/27/2025, https://ccga.io/index.php/BRST5:Adenoid cystic carcinoma.