1. Integration of Genomic and Transcriptomic Features in Pancreatic Cancer Reveals Increased Cell Cycle Progression in Metastases
- Author
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Bradly G. Wouters, Sulaiman Nanji, Stefano Serra, George Zogopoulos, Joan Miguel Romero, Michelle Chan-Seng-Yue, Calvin Law, Dianne E. Chadwick, Paul M. Krzyzanowski, Lars G.T. Jorgensen, Jenna Eagles, Jessica Miller, Anna Dodd, David W. Hedley, Alyssa L. Smith, Amy Zhang, Grainne M. O'Kane, Xuemei Luo, Sandra Fischer, Sara Hafezi Bakhtiari, Sheng-Ben Liang, Julie M. Wilson, Gavin W. Wilson, Steven Gallinger, Ilinca Lungu, Mathieu Lemire, Jennifer J. Knox, Gloria M. Petersen, Talia Golan, Ayelet Borgida, Heather Armstrong, Ashton A. Connor, Sean P. Cleary, Prashant Bavi, Faiyaz Notta, Michael H.A. Roehrl, Faridah Mbabaali, Derin Caglar, Gun Ho Jang, John M. S. Bartlett, Michael A. Hollingsworth, Robert E. Denroche, Daniele Merico, and Sarah P. Thayer
- Subjects
Chromosomal translocation ,Cell cycle ,Biology ,Hypoxia (medical) ,medicine.disease ,law.invention ,Transcriptome ,law ,Pancreatic cancer ,medicine ,Cancer research ,Suppressor ,medicine.symptom ,Gene ,Regulator gene - Abstract
We integrated clinical, genomic and transcriptomic data from 217 primaries and 101 metastases from 289 patients to characterize progression of pancreatic ductal adenocarcinoma. Driver genes alterations, mutational and expression-based signatures were mostly preserved, and discordances implied Halstedian tumour spread. Cell cycle progression increased with sequential inactivation of tumour suppressors, yet remained higher in metastases, perhaps driven by cell cycle regulatory gene mutations. Half of the cases were hypoxic by expression markers, overlapping with molecular subtypes. Inter-tumoural heterogeneity showed conserved truncations, inversions and translocations and therefore likely driver events. Multiple synchronous and metachronous PDAC arising in the same patients were actually intra-parenchymal metastases, and not independent primary tumours. Established clinical co-variates dominated survival analyses, though cell cycle progression, hypoxia and inter-tumoural heterogeneity may inform clinical practice.
- Published
- 2018