Faculty Collaboration Database

Profiling of 149 Salivary Duct Carcinomas, Carcinoma Ex Pleomorphic Adenomas, and Adenocarcinomas, Not Otherwise Specified Reveals Actionable Genomic Alterations. Clin Cancer Res 2016 Dec 15;22(24):6061-6068

Date

06/24/2016

Pubmed ID

27334835

DOI

10.1158/1078-0432.CCR-15-2568

Scopus ID

2-s2.0-85007020561 (requires institutional sign-in at Scopus site)   99 Citations

Abstract

PURPOSE: We sought to identify genomic alterations (GA) in salivary gland adenocarcinomas, not otherwise specified (NOS), salivary duct carcinomas (SDC), carcinoma ex pleomorphic adenoma (ca ex PA), and salivary carcinoma, NOS.

EXPERIMENTAL DESIGN: DNA was extracted from 149 tumors. Comprehensive genomic profiling (CGP) was performed on hybridization-captured adaptor ligation-based libraries of 182 or 315 cancer-related genes plus introns from 14 or 28 genes frequently rearranged for cancer and evaluated for all classes of GAs.

RESULTS: A total of 590 GAs were found in 157 unique genes (mean 3.9/tumor). GAs in the PI3K/AKT/mTOR pathway were more common in SDC (53.6%) than other histologies (P = 0.019) Cyclin-dependent kinase GAs varied among all histotypes: adenocarcinoma, NOS (34.6%); SDC (12.2%); ca ex PA (16.7%); carcinoma, NOS (31.2%; P = 0.043). RAS GAs were observed: adenocarcinoma, NOS (17.3%); SDC (26.8%); ca ex PA (4.2%); and carcinoma, NOS (9.4%; P = 0.054). ERBB2 GAs, including amplifications and mutations, were common: adenocarcinoma, NOS (13.5%); SDC (26.8%); ca ex PA (29.2%); carcinoma, NOS (18.8; P = 0.249). Other notable GAs include TP53 in >45% of each histotype; NOTCH1: adenocarcinoma, NOS (7.7%), ca ex PA (8.3%), carcinoma, NOS (21.6%); NF1: adenocarcinoma, NOS (9.6%), SDC (17.1%), carcinoma, NOS (18.8%). RET fusions were identified in one adenocarcinoma, NOS (CCDC6-RET) and two SDCs (NCOA4-RET). Clinical responses were observed in patients treated with anti-HER2 and anti-RET-targeted therapies.

CONCLUSIONS: CGP of salivary adenocarcinoma, NOS, SDCs, ca ex PA, and carcinoma, NOS revealed diverse GAs that may lead to novel treatment options. Clin Cancer Res; 22(24); 6061-8. ©2016 AACR.

Author List

Wang K, Russell JS, McDermott JD, Elvin JA, Khaira D, Johnson A, Jennings TA, Ali SM, Murray M, Marshall C, Oldham DS, Washburn D, Wong SJ, Chmielecki J, Yelensky R, Lipson D, Miller VA, Stephens PJ, Serracino HS, Ross JS, Bowles DW

Author

Stuart J. Wong MD Center Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Adenoma, Pleomorphic
Carcinoma, Ductal
Female
Gene Rearrangement
Genomics
Humans
Male
Mutation
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
Receptor, ErbB-2
Salivary Ducts
Salivary Gland Neoplasms
TOR Serine-Threonine Kinases