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Integration of Genomic and Transcriptional Features in Pancreatic Cancer Reveals Increased Cell Cycle Progression in Metastases.
Connor, Ashton A; Denroche, Robert E; Jang, Gun Ho; Lemire, Mathieu; Zhang, Amy; Chan-Seng-Yue, Michelle; Wilson, Gavin; Grant, Robert C; Merico, Daniele; Lungu, Ilinca; Bartlett, John M S; Chadwick, Dianne; Liang, Sheng-Ben; Eagles, Jenna; Mbabaali, Faridah; Miller, Jessica K; Krzyzanowski, Paul; Armstrong, Heather; Luo, Xuemei; Jorgensen, Lars G T; Romero, Joan M; Bavi, Prashant; Fischer, Sandra E; Serra, Stefano; Hafezi-Bakhtiari, Sara; Caglar, Derin; Roehrl, Michael H A; Cleary, Sean; Hollingsworth, Michael A; Petersen, Gloria M; Thayer, Sarah; Law, Calvin H L; Nanji, Sulaiman; Golan, Talia; Smith, Alyssa L; Borgida, Ayelet; Dodd, Anna; Hedley, David; Wouters, Bradly G; O'Kane, Grainne M; Wilson, Julie M; Zogopoulos, George; Notta, Faiyaz; Knox, Jennifer J; Gallinger, Steven.
Affiliation
  • Connor AA; PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada.
  • Denroche RE; PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
  • Jang GH; PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
  • Lemire M; PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
  • Zhang A; PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
  • Chan-Seng-Yue M; PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
  • Wilson G; PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
  • Grant RC; PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Wallace McCain Centre for Pancreatic Cancer, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
  • Merico D; Deep Genomics, Inc., Toronto, ON M5G 1L7, Canada; The Centre for Applied Genomics (TCAG), The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
  • Lungu I; Diagnostic Development, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
  • Bartlett JMS; Diagnostic Development, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
  • Chadwick D; UHN Biobank, University Health Network, Toronto, ON M5G 2M9, Canada.
  • Liang SB; UHN Biobank, University Health Network, Toronto, ON M5G 2M9, Canada.
  • Eagles J; Genomics, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
  • Mbabaali F; Genomics, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
  • Miller JK; Genomics, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
  • Krzyzanowski P; Genomics, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
  • Armstrong H; Genome Sequence Informatics, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
  • Luo X; Genome Sequence Informatics, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
  • Jorgensen LGT; Genome Sequence Informatics, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
  • Romero JM; PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
  • Bavi P; PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, University Health Network, Toronto, ON M5G 2M9, Canada.
  • Fischer SE; Department of Pathology, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, University Health Network, Toronto, ON M5G 2M9, Canada.
  • Serra S; Department of Pathology, University Health Network, Toronto, ON M5G 2M9, Canada.
  • Hafezi-Bakhtiari S; Department of Pathology, University Health Network, Toronto, ON M5G 2M9, Canada.
  • Caglar D; Department of Pathology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
  • Roehrl MHA; UHN Biobank, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Pathology, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Medic
  • Cleary S; Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA.
  • Hollingsworth MA; University of Nebraska Medical Centre, Omaha, NE 68198, USA.
  • Petersen GM; Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
  • Thayer S; University of Nebraska Medical Centre, Omaha, NE 68198, USA; Massachusetts General Hospital, Boston, MA 02114, USA.
  • Law CHL; Department of Surgery, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada.
  • Nanji S; Department of Surgery, Kingston General Hospital, Kingston, ON K7L 2V7, Canada.
  • Golan T; Pancreatic Cancer Translational Research Laboratory, Oncology Institute, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Smith AL; Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
  • Borgida A; Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
  • Dodd A; Wallace McCain Centre for Pancreatic Cancer, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
  • Hedley D; Division of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
  • Wouters BG; Division of Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
  • O'Kane GM; PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Wallace McCain Centre for Pancreatic Cancer, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
  • Wilson JM; PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
  • Zogopoulos G; Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; Goodman Cancer Research Centre, Montreal, QC H3A 1A3, Canada.
  • Notta F; PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Division of Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G
  • Knox JJ; PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Wallace McCain Centre for Pancreatic Cancer, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
  • Gallinger S; PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada; Hepatobiliary/Pancreatic Surgical Oncology Program, University Health Network, Toronto, ON M5G 2M9, Canada; Lunenf
Cancer Cell ; 35(2): 267-282.e7, 2019 02 11.
Article in En | MEDLINE | ID: mdl-30686769
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.
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Full text: 1 Database: MEDLINE Main subject: Pancreatic Neoplasms / Transcription, Genetic / Biomarkers, Tumor / Gene Expression Regulation, Neoplastic / Cell Cycle / Cell Movement / Carcinoma, Pancreatic Ductal / Cell Proliferation / Liver Neoplasms / Mutation Type of study: Clinical_trials Limits: Animals / Humans Country/Region as subject: America do norte / Asia Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2019 Type: Article Affiliation country: Canada
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Full text: 1 Database: MEDLINE Main subject: Pancreatic Neoplasms / Transcription, Genetic / Biomarkers, Tumor / Gene Expression Regulation, Neoplastic / Cell Cycle / Cell Movement / Carcinoma, Pancreatic Ductal / Cell Proliferation / Liver Neoplasms / Mutation Type of study: Clinical_trials Limits: Animals / Humans Country/Region as subject: America do norte / Asia Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2019 Type: Article Affiliation country: Canada