Integration of genomic and transcriptional features in pancreatic cancer reveals increased cell cycle progression in metastases Journal Article
| Authors: | Connor, A. A.; Denroche, R. E.; Jang, G. H.; Lemire, M.; Zhang, A.; Chan-Seng-Yue, M.; Wilson, G.; Grant, R. C.; Merico, D.; Lungu, I.; Bartlett, J. M. S.; Chadwick, D.; Liang, S. B.; Eagles, J.; Mbabaali, F.; Miller, J. K.; Krzyzanowski, P.; Armstrong, H.; Luo, X.; Jorgensen, L. G. T.; Romero, J. M.; Bavi, P.; Fischer, S. E.; Serra, S.; Hafezi-Bakhtiari, S.; Caglar, D.; Roehrl, M. H. A.; Cleary, S.; Hollingsworth, M. A.; Petersen, G. M.; Thayer, S.; Law, C. H. L.; Nanji, S.; Golan, T.; Smith, A. L.; Borgida, A.; Dodd, A.; Hedley, D.; Wouters, B. G.; O'Kane, G. M.; Wilson, J. M.; Zogopoulos, G.; Notta, F.; Knox, J. J.; Gallinger, S. |
| Article 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. © 2018 Elsevier Inc. |
| Keywords: | adult; human tissue; aged; middle aged; gene mutation; human cell; cell cycle progression; metastasis; gene expression; genetic transcription; transcriptomics; age; hypoxia; cell migration; pancreas adenocarcinoma; genome; metastases; tumor hypoxia; rna sequence; pancreatic ductal adenocarcinoma; cancer prognosis; whole-genome sequencing; human; priority journal; article; rna sequencing; mutational signatures; driver genes |
| Journal Title: | Cancer Cell |
| Volume: | 35 |
| Issue: | 2 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2019-02-11 |
| Start Page: | 267 |
| End Page: | 282.e7 |
| Language: | English |
| DOI: | 10.1016/j.ccell.2018.12.010 |
| PUBMED: | 30686769 |
| PROVIDER: | scopus |
| PMCID: | PMC6398439 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2019 -- Source: Scopus |
