[HTML][HTML] Whole exome sequencing of adenoid cystic carcinoma

PJ Stephens, HR Davies, Y Mitani… - The Journal of …, 2013 - Am Soc Clin Investig
PJ Stephens, HR Davies, Y Mitani, P Van Loo, A Shlien, PS Tarpey, E Papaemmanuil
The Journal of clinical investigation, 2013Am Soc Clin Investig
Adenoid cystic carcinoma (ACC) is a rare malignancy that can occur in multiple organ sites
and is primarily found in the salivary gland. While the identification of recurrent fusions of the
MYB-NFIB genes have begun to shed light on the molecular underpinnings, little else is
known about the molecular genetics of this frequently fatal cancer. We have undertaken
exome sequencing in a series of 24 ACC to further delineate the genetics of the disease. We
identified multiple mutated genes that, combined, implicate chromatin deregulation in half of …
Adenoid cystic carcinoma (ACC) is a rare malignancy that can occur in multiple organ sites and is primarily found in the salivary gland. While the identification of recurrent fusions of the MYB-NFIB genes have begun to shed light on the molecular underpinnings, little else is known about the molecular genetics of this frequently fatal cancer. We have undertaken exome sequencing in a series of 24 ACC to further delineate the genetics of the disease. We identified multiple mutated genes that, combined, implicate chromatin deregulation in half of cases. Further, mutations were identified in known cancer genes, including PIK3CA, ATM, CDKN2A, SF3B1, SUFU, TSC1, and CYLD. Mutations in NOTCH1/2 were identified in 3 cases, and we identify the negative NOTCH signaling regulator, SPEN, as a new cancer gene in ACC with mutations in 5 cases. Finally, the identification of 3 likely activating mutations in the tyrosine kinase receptor FGFR2, analogous to those reported in ovarian and endometrial carcinoma, point to potential therapeutic avenues for a subset of cases.
The Journal of Clinical Investigation