Format

Send to

Choose Destination
Cancer Res. 2016 Sep 1;76(17):5092-102. doi: 10.1158/0008-5472.CAN-16-0658. Epub 2016 Aug 3.

The Genomic Landscape of Pancreatic and Periampullary Adenocarcinoma.

Author information

1
Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. Department for Environmental Health and Science, University College of Southeast Norway, Bø, Norway.
2
Wellcome Trust Sanger Institute, Hinxton, United Kingdom. Department of Cancer Genomics, Big Data Institute, University of Oxford, Oxford, United Kingdom.
3
Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. Department of Pathology, Oslo University Hospital, Oslo, Norway.
4
Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway.
5
Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway. Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
6
Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
7
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
8
Department of Computer Science, University of Oslo, Oslo, Norway.
9
Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
10
Department of Oncology, Oslo University Hospital, Oslo, Norway. Akershus University Hospital, Nordbyhagen, Norway.
11
The Francis Crick Institute, London, United Kingdom. Department of Human Genetics, University of Leuven, Leuven, Belgium.
12
Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. Department for Environmental Health and Science, University College of Southeast Norway, Bø, Norway. Elin.Kure@rr-research.no.

Abstract

Despite advances in diagnostics, less than 5% of patients with periampullary tumors experience an overall survival of five years or more. Periampullary tumors are neoplasms that arise in the vicinity of the ampulla of Vater, an enlargement of liver and pancreas ducts where they join and enter the small intestine. In this study, we analyzed copy number aberrations using Affymetrix SNP 6.0 arrays in 60 periampullary adenocarcinomas from Oslo University Hospital to identify genome-wide copy number aberrations, putative driver genes, deregulated pathways, and potential prognostic markers. Results were validated in a separate cohort derived from The Cancer Genome Atlas Consortium (n = 127). In contrast to many other solid tumors, periampullary adenocarcinomas exhibited more frequent genomic deletions than gains. Genes in the frequently codeleted region 17p13 and 18q21/22 were associated with cell cycle, apoptosis, and p53 and Wnt signaling. By integrating genomics and transcriptomics data from the same patients, we identified CCNE1 and ERBB2 as candidate driver genes. Morphologic subtypes of periampullary adenocarcinomas (i.e., pancreatobiliary or intestinal) harbor many common genomic aberrations. However, gain of 13q and 3q, and deletions of 5q were found specific to the intestinal subtype. Our study also implicated the use of the PAM50 classifier in identifying a subgroup of patients with a high proliferation rate, which had impaired survival. Furthermore, gain of 18p11 (18p11.21-23, 18p11.31-32) and 19q13 (19q13.2, 19q13.31-32) and subsequent overexpression of the genes in these loci were associated with impaired survival. Our work identifies potential prognostic markers for periampullary tumors, the genetic characterization of which has lagged. Cancer Res; 76(17); 5092-102.

PMID:
27488532
DOI:
10.1158/0008-5472.CAN-16-0658
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center