BRST5:Adenoid cystic carcinoma: Difference between revisions

|Fusion transcripts most commonly join exon 8 or exon 14 of ''MYB'' with exon 9 of ''NFIB'' and result in overexpression of ''MYB''.<ref name=":2">{{Cite journal|last=Persson|first=Marta|last2=Andrén|first2=Ywonne|last3=Mark|first3=Joachim|last4=Horlings|first4=Hugo M.|last5=Persson|first5=Fredrik|last6=Stenman|first6=Göran|date=2009-11-03|title=Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck|url=https://pubmed.ncbi.nlm.nih.gov/19841262|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=106|issue=44|pages=18740–18744|doi=10.1073/pnas.0909114106|issn=1091-6490|pmc=2773970|pmid=19841262}}</ref><ref name=":1">{{Cite journal|last=Brill|first=Louis B.|last2=Kanner|first2=William A.|last3=Fehr|first3=André|last4=Andrén|first4=Ywonne|last5=Moskaluk|first5=Christopher A.|last6=Löning|first6=Thomas|last7=Stenman|first7=Göran|last8=Frierson|first8=Henry F.|date=2011-09|title=Analysis of MYB expression and MYB-NFIB gene fusions in adenoid cystic carcinoma and other salivary neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/21572406|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=24|issue=9|pages=1169–1176|doi=10.1038/modpathol.2011.86|issn=1530-0285|pmid=21572406}}</ref><ref name=":3">{{Cite journal|last=D'Alfonso|first=Timothy M.|last2=Mosquera|first2=Juan Miguel|last3=MacDonald|first3=Theresa Y.|last4=Padilla|first4=Jessica|last5=Liu|first5=Yi-Fang|last6=Rubin|first6=Mark A.|last7=Shin|first7=Sandra J.|date=2014-11|title=MYB-NFIB gene fusion in adenoid cystic carcinoma of the breast with special focus paid to the solid variant with basaloid features|url=https://pubmed.ncbi.nlm.nih.gov/25217885|journal=Human Pathology|volume=45|issue=11|pages=2270–2280|doi=10.1016/j.humpath.2014.07.013|issn=1532-8392|pmid=25217885}}</ref><ref name=":4">{{Cite journal|last=Mitani|first=Yoshitsugu|last2=Liu|first2=Bin|last3=Rao|first3=Pulivarthi H.|last4=Borra|first4=Vishnupriya J.|last5=Zafereo|first5=Mark|last6=Weber|first6=Randal S.|last7=Kies|first7=Merrill|last8=Lozano|first8=Guillermina|last9=Futreal|first9=P. Andrew|date=2016-02-01|title=Novel MYBL1 Gene Rearrangements with Recurrent MYBL1-NFIB Fusions in Salivary Adenoid Cystic Carcinomas Lacking t(6;9) Translocations|url=https://pubmed.ncbi.nlm.nih.gov/26631609|journal=Clinical Cancer Research: An Official Journal of the American Association for Cancer Research|volume=22|issue=3|pages=725–733|doi=10.1158/1078-0432.CCR-15-2867-T|issn=1557-3265|pmc=4807116|pmid=26631609}}</ref> Fusions translocate super-enhancers in the partner gene to ''MYB''.<ref>{{Cite journal|last=Drier|first=Yotam|last2=Cotton|first2=Matthew J.|last3=Williamson|first3=Kaylyn E.|last4=Gillespie|first4=Shawn M.|last5=Ryan|first5=Russell J. H.|last6=Kluk|first6=Michael J.|last7=Carey|first7=Christopher D.|last8=Rodig|first8=Scott J.|last9=Sholl|first9=Lynette M.|date=2016-03|title=An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma|url=https://pubmed.ncbi.nlm.nih.gov/26829750|journal=Nature Genetics|volume=48|issue=3|pages=265–272|doi=10.1038/ng.3502|issn=1546-1718|pmc=4767593|pmid=26829750}}</ref> Fusion transcripts lack ''MYB'' exon 15 including the 3' UTR, which contains target sites for microRNAs that negatively regulate ''MYB.''<ref name=":2" />  

|Some breast cancers express more than one ''MYB''::''NFIB'' transcript or splice variant<ref name=":1" /><ref name=":3" />

|''MYBL1''

|''MYBL1''::''NFIB''

|Fusions most commonly join exon 8 or exon 14 of ''MYBL1'' with exon 11 of ''NFIB.''<ref name=":4" />

|t(8;9)(q13.1;p23)

|Rare

|D

|Yes (WHO)

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''.<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 />

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>