BRST5:Adenoid cystic carcinoma: Difference between revisions

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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>

!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T

|<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> ''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)

 

''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).

 

 

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> 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.

 

 

 

|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" />

!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'''

!'''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!!'''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'''

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