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BRST5:Adenoid Cystic Carcinoma (view source)
Revision as of 00:06, 6 November 2023
, 00:06, 6 November 2023→Genes and Main Pathways Involved
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|''NOTCH1'', ''NOTCH2'', and ''NOTCH3''; sequence variants <ref name=":5">{{Cite journal|last=Massé|first=Julie|last2=Truntzer|first2=Caroline|last3=Boidot|first3=Romain|last4=Khalifa|first4=Emmanuel|last5=Pérot|first5=Gaëlle|last6=Velasco|first6=Valérie|last7=Mayeur|first7=Laétitia|last8=Billerey-Larmonier|first8=Claire|last9=Blanchard|first9=Larry|date=2020-06|title=Solid-type adenoid cystic carcinoma of the breast, a distinct molecular entity enriched in NOTCH and CREBBP mutations|url=https://pubmed.ncbi.nlm.nih.gov/31857685|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=33|issue=6|pages=1041–1055|doi=10.1038/s41379-019-0425-3|issn=1530-0285|pmid=31857685}}</ref>
|''NOTCH1'', ''NOTCH2'', and ''NOTCH3''; sequence variants <ref name=":5">{{Cite journal|last=Massé|first=Julie|last2=Truntzer|first2=Caroline|last3=Boidot|first3=Romain|last4=Khalifa|first4=Emmanuel|last5=Pérot|first5=Gaëlle|last6=Velasco|first6=Valérie|last7=Mayeur|first7=Laétitia|last8=Billerey-Larmonier|first8=Claire|last9=Blanchard|first9=Larry|date=2020-06|title=Solid-type adenoid cystic carcinoma of the breast, a distinct molecular entity enriched in NOTCH and CREBBP mutations|url=https://pubmed.ncbi.nlm.nih.gov/31857685|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=33|issue=6|pages=1041–1055|doi=10.1038/s41379-019-0425-3|issn=1530-0285|pmid=31857685}}</ref>
|Loss of function
|Gain of function
|22-28% solid basaloid subtype <ref name=":8" /> <ref name=":5" />
|22-28% solid basaloid subtype <ref name=":8" /> <ref name=":5" />
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|Mostly solid basaloid subtype, with poorer prognosis
|Mostly solid basaloid subtype, with poorer prognosis
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|''KDM6A''; inactivating sequence variants
|''KDM6A''; inactivating sequence variants
|Loss of function
|Loss of function
|22% solid basaloid subtype in one study <ref name=":8" />
|22% solid basaloid subtype in one study <ref name=":8" />
|Promotes cellular proliferation
|Promotes cellular proliferation
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A study of adenoid cystic carcinoma of salivary glands by Drier and others delineates the mechanism of MYB gene pathway upregulation via rearrangements that increase MYB expression. ''MYB'' rearrangements typically juxtapose ''MYB'' with strong enhancers in regions downstream of ''NFIB, TGFBR3'' and ''RAD51B.'' Gene fusions most often occur on the 3' side of ''MYB'', a subset of gene fusions occur on the 5' side, and all serve to bring the ''MYB'' gene locus close to strong enhancer elements, thus upregulating MYB expression. The authors note that TP63 signaling is active in the myoepithelial component of low grade adenoid cystic carcinomas, while Notch signaling is active in luminal epithelial components. Furthermore, the authors suggest that Notch pathway mutations may underlie the switch to solid histology and the more aggressive clinical course of these tumors.<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>
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==