Characterization of genome-wide copy number aberrations in colonic mixed adenoneuroendocrine carcinoma and neuroendocrine carcinoma reveals recurrent amplification of PTGER4 and MYC genes

Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Namita Sinha, Daniel Gaston, Daniel Manders, Marissa Goudie, Makoto Matsuoka, Tao Xie, Weei-Yuarn Huang
Colonic Mixed adenoneuroendocrine Carcinoma (MANEC) is an aggressive neoplasm with worse prognosis compared to adenocarcinoma. To gain a better understanding of the molecular features of colonic MANEC, we characterized the genome-wide copy number aberrations (CNA) of 14 MANECs and 5 neuroendocrine carcinomas using the OncoScan FFPE assay. Compared to 269 colonic adenocarcinomas, 19 of 42 chromosomal arms of MANEC exhibited a similar frequency of major aberrant events as adenocarcinomas, and 13 chromosomal arms exhibited a higher frequency of copy number gains. Among them, the most significant chromosomal arms were 5p (77% vs. 13%, P=1.2E-05) and 8q (85% vs. 33%, P=0.0018). The genomic identification of significant targets in cancers (GISTIC) algorithm identified seven peaks that drive the tumorgenesis of MANEC. For all except 5p13.1, the peaks largely overlapped with those of adenocarcinoma. Two tumors exhibited MYC amplification localized in 8q24.21 and two tumors exhibited PTGER4 amplification localized in 5p13.1. A total of eight tumors exhibited high copy number gain of PTGER4 and/or MYC. While the frequency of MYC amplification was similar to adenocarcinoma (10.5% vs. 4%, P=0.2), the frequency of PTGER4 amplification was higher than adenocarcinoma (10.5% vs. 0.3%, P=0.01). Our study demonstrates similar, but also distinct, CNAs in MANEC compared to adenocarcinoma and suggests an important role for the MYC pathway of colonic carcinoma with neuroendocrine differentiation. The discovery of recurrent PTGER4 amplification implies a potential of exploring targeting therapy to the prostaglandin synthesis pathways in a subset of these tumors.



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