@article{b9854a6e0da3494b86ab5eb84a2d74a4,
title = "Integration of Genomic and Transcriptional Features in Pancreatic Cancer Reveals Increased Cell Cycle Progression in Metastases",
abstract = "We integrated clinical, genomic, and transcriptomic data from 224 primaries and 95 metastases from 289 patients to characterize progression of pancreatic ductal adenocarcinoma (PDAC). Driver gene alterations and mutational and expression-based signatures were preserved, with truncations, inversions, and translocations most conserved. Cell cycle progression (CCP) increased with sequential inactivation of tumor suppressors, yet remained higher in metastases, perhaps driven by cell cycle regulatory gene variants. Half of the cases were hypoxic by expression markers, overlapping with molecular subtypes. Paired tumor heterogeneity showed cancer cell migration by Halstedian progression. Multiple PDACs arising synchronously and metachronously in the same pancreas were actually intra-parenchymal metastases, not independent primary tumors. Established clinical co-variates dominated survival analyses, although CCP and hypoxia may inform clinical practice.",
keywords = "RNA sequencing, cell cycle progression, driver genes, hypoxia, metastases, mutational signatures, pancreatic ductal adenocarcinoma, whole-genome sequencing",
author = "Connor, {Ashton A.} and Denroche, {Robert E.} and Jang, {Gun Ho} and Mathieu Lemire and Amy Zhang and Michelle Chan-Seng-Yue and Gavin Wilson and Grant, {Robert C.} and Daniele Merico and Ilinca Lungu and Bartlett, {John M.S.} and Dianne Chadwick and Liang, {Sheng Ben} and Jenna Eagles and Faridah Mbabaali and Miller, {Jessica K.} and Paul Krzyzanowski and Heather Armstrong and Xuemei Luo and Jorgensen, {Lars G.T.} and Romero, {Joan M.} and Prashant Bavi and Fischer, {Sandra E.} and Stefano Serra and Sara Hafezi-Bakhtiari and Derin Caglar and Roehrl, {Michael H.A.} and Sean Cleary and Hollingsworth, {Michael A.} and Petersen, {Gloria M.} and Sarah Thayer and Law, {Calvin H.L.} and Sulaiman Nanji and Talia Golan and Smith, {Alyssa L.} and Ayelet Borgida and Anna Dodd and David Hedley and Wouters, {Bradly G.} and O'Kane, {Grainne M.} and Wilson, {Julie M.} and George Zogopoulos and Faiyaz Notta and Knox, {Jennifer J.} and Steven Gallinger",
note = "Funding Information: This study was conducted with the support of the Ontario Institute for Cancer Research (OICR, PanCuRx Translational Research Initiative) through funding provided by the Government of Ontario (Ministry of Research, Innovation, and Science), the Wallace McCain Centre for Pancreatic Cancer supported by the Princess Margaret Cancer Foundation, and charitable donations from the Canadian Friends of the Hebrew University (Alex U. Soyka), the Pancreatic Cancer Canada Foundation, and the Canadian Cancer Society Research Institute. G.Z. is a clinical research scholar of the Fonds de recherche du Qu{\'e}bec – Sant{\'e}. G.M.P. is supported by a SPORE grant from the National Institutes of Health (NCI grant P50CA102701). Funding Information: This study was conducted with the support of the Ontario Institute for Cancer Research (OICR, PanCuRx Translational Research Initiative) through funding provided by the Government of Ontario (Ministry of Research, Innovation, and Science), the Wallace McCain Centre for Pancreatic Cancer supported by the Princess Margaret Cancer Foundation , and charitable donations from the Canadian Friends of the Hebrew University (Alex U. Soyka), the Pancreatic Cancer Canada Foundation , and the Canadian Cancer Society Research Institute . G.Z. is a clinical research scholar of the Fonds de recherche du Qu{\'e}bec – Sant{\'e}. G.M.P. is supported by a SPORE grant from the National Institutes of Health ( NCI grant P50CA102701 ). Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2019",
month = feb,
day = "11",
doi = "10.1016/j.ccell.2018.12.010",
language = "English (US)",
volume = "35",
pages = "267--282.e7",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",
}