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Cancer Prev Res (Phila). 2016 Apr;9(4):265-74. doi: 10.1158/1940-6207.CAPR-15-0316. Epub 2016 Feb 9.

Whole-Genome Sequencing of Salivary Gland Adenoid Cystic Carcinoma.

Author information

1
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
2
Institute for Basic Biomedical Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
3
Personal Genome Diagnostics, Baltimore, Maryland.
4
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
5
Johns Hopkins Institute for Computational Medicine and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland.
6
Johns Hopkins Institute for Computational Medicine and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland. Department of Oncology, John Hopkins University School of Medicine, Baltimore, Maryland.
7
Department of Oncology Biostatistics & Bioinformatics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
8
Department of Oncology, John Hopkins University School of Medicine, Baltimore, Maryland.
9
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. Milton J. Dance Jr. Head and Neck Cancer Center, Greater Baltimore Medical Center, Baltimore, Maryland.
10
Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
11
Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. nishant.agrawal@uchicago.edu nagrawal@jhmi.edu Patrick.Ha@ucsf.edu vogelbe@jhmi.edu.
12
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. Milton J. Dance Jr. Head and Neck Cancer Center, Greater Baltimore Medical Center, Baltimore, Maryland. nishant.agrawal@uchicago.edu nagrawal@jhmi.edu Patrick.Ha@ucsf.edu vogelbe@jhmi.edu.
13
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Surgery, Section of Otolaryngology-Head and Neck Surgery, The University of Chicago, Chicago, Illinois States. nishant.agrawal@uchicago.edu nagrawal@jhmi.edu Patrick.Ha@ucsf.edu vogelbe@jhmi.edu.

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.

PMID:
26862087
PMCID:
PMC4818686
DOI:
10.1158/1940-6207.CAPR-15-0316
[Indexed for MEDLINE]
Free PMC Article

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