Whole-Genome Sequencing of Salivary Gland Adenoid Cystic Carcinoma
Document Type
Article
Publication Title
Cancer Prevention Research
Abstract
Adenoid cystic carcinomas (ACC) of the salivary glands are challenging to understand, treat, and cure. To better understand the genetic alterations underlying the pathogenesis of these tumors, we performed comprehensive genome analyses of 25 fresh-frozen tumors, including whole-genome sequencing and expression and pathway analyses. In addition to the well-described MYB-NFIB fusion that was found in 11 tumors (44%), we observed five different rearrangements involving the NFIB transcription factor gene in seven tumors (28%). Taken together, NFIB translocations occurred in 15 of 25 samples (60%, 95% CI, 41%-77%). In addition, mRNA expression analysis of 17 tumors revealed overexpression of NFIB in ACC tumors compared with normal tissues (P = 0.002). There was no difference in NFIB mRNA expression in tumors with NFIB fusions compared with those without. We also report somatic mutations of genes involved in the axonal guidance and Rho family signaling pathways. Finally, we confirm previously described alterations in genes related to chromatin regulation and Notch signaling. Our findings suggest a separate role for NFIB in ACC oncogenesis and highlight important signaling pathways for future functional characterization and potential therapeutic targeting.
First Page
265
Last Page
274
DOI
https://doi.org/10.1158/1940-6207.capr-15-0316
Publication Date
Spring 4-2016
Recommended Citation
Rettig EM, Talbot CC Jr, Sausen M, Jones S, Bishop JA, Wood LD, Tokheim C, Niknafs N, Karchin R, Fertig EJ, Wheelan SJ, Marchionni L, Considine M, Ling S, Fakhry C, Papadopoulos N, Kinzler KW, Vogelstein B, Ha PK, Agrawal N. Whole-Genome Sequencing of Salivary Gland Adenoid Cystic Carcinoma. Cancer Prev Res (Phila). 2016 Apr;9(4):265-74. doi: 10.1158/1940-6207.CAPR-15-0316. Epub 2016 Feb 9. Erratum in: Cancer Prev Res (Phila). 2018 Apr;11(4):249. PMID: 26862087; PMCID: PMC4818686.
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