BRST5:Adenoid cystic carcinoma
Primary Author(s)*
Jun Liao, PhD, Columbia University and Katherine Geiersbach, MD, Mayo Clinic - Rochester
WHO Classification of Disease
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| Structure | Disease |
|---|---|
| Book | |
| Category | |
| Family | |
| Type | |
| Subtype(s) |
WHO Essential and Desirable Genetic Diagnostic Criteria
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| 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 more common 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] | |||
| FBXW7 | Inactivating | Tumor Suppressor Gene | Rare[7] | |||
| SMARCA5 | Inactivating | Tumor Suppressor Gene | Rare[7] | |||
| SF3B1 | Activating | Other | Rare[7] | |||
| FGFR2 | Activating | Oncogene | Rare[7] | |||
| MTOR | Activating | 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
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Genes and Main Pathways Involved
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| 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 |
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.[10]
Familial Forms
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Additional Information
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Links
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Notes
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Prior Author(s):
References
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- ↑ 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.
- ↑ 2.0 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) - ↑ 3.0 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) - ↑ 4.0 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.
- ↑ 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) - ↑ 6.0 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) - ↑ 7.0 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) - ↑ 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) - ↑ 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) - ↑ 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)