دورية أكاديمية
The Genomic Landscape of Pancreatic and Periampullary Adenocarcinoma.
| العنوان: | The Genomic Landscape of Pancreatic and Periampullary Adenocarcinoma. |
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| المؤلفون: | Sandhu V; 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., Wedge DC; Wellcome Trust Sanger Institute, Hinxton, United Kingdom. Department of Cancer Genomics, Big Data Institute, University of Oxford, Oxford, United Kingdom., Bowitz Lothe IM; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. Department of Pathology, Oslo University Hospital, Oslo, Norway., Labori KJ; Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway., Dentro SC; Wellcome Trust Sanger Institute, Hinxton, United Kingdom. Department of Cancer Genomics, Big Data Institute, University of Oxford, Oxford, United Kingdom., Buanes T; Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway. Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Skrede ML; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Dalsgaard AM; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Munthe E; Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Myklebost O; Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Lingjærde OC; Department of Computer Science, University of Oslo, Oslo, Norway., Børresen-Dale AL; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Ikdahl T; Department of Oncology, Oslo University Hospital, Oslo, Norway. Akershus University Hospital, Nordbyhagen, Norway., Van Loo P; The Francis Crick Institute, London, United Kingdom. Department of Human Genetics, University of Leuven, Leuven, Belgium., Nord S; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Kure EH; 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. |
| المصدر: | Cancer research [Cancer Res] 2016 Sep 01; Vol. 76 (17), pp. 5092-102. Date of Electronic Publication: 2016 Aug 03. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-7445 (Electronic) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Baltimore, Md. : American Association for Cancer Research Original Publication: Chicago [etc.] |
| مواضيع طبية MeSH: | Adenocarcinoma/*genetics , Carcinoma, Pancreatic Ductal/*genetics , Common Bile Duct Neoplasms/*genetics , Pancreatic Neoplasms/*genetics, Adenocarcinoma/mortality ; Aged ; Ampulla of Vater ; Carcinoma, Pancreatic Ductal/mortality ; Common Bile Duct Neoplasms/mortality ; DNA Copy Number Variations ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Pancreatic Neoplasms/mortality |
| مستخلص: | 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. ©2016 AACR. (©2016 American Association for Cancer Research.) |
| تواريخ الأحداث: | Date Created: 20160805 Date Completed: 20170724 Latest Revision: 20180128 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1158/0008-5472.CAN-16-0658 |
| PMID: | 27488532 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1538-7445 |
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| DOI: | 10.1158/0008-5472.CAN-16-0658 |