Genome-wide characterization of pancreatic adenocarcinoma patients using next generation sequencing.

PLoS ONE. 2012;7(10):e43192 DOI 10.1371/journal.pone.0043192


Journal Homepage

Journal Title: PLoS ONE

ISSN: 1932-6203 (Online)

Publisher: Public Library of Science (PLoS)

LCC Subject Category: Medicine | Science

Country of publisher: United States

Language of fulltext: English

Full-text formats available: PDF, HTML, XML



Winnie S Liang

David W Craig

John Carpten

Mitesh J Borad

Michael J Demeure

Glen J Weiss

Tyler Izatt

Shripad Sinari

Alexis Christoforides

Jessica Aldrich

Ahmet Kurdoglu

Michael Barrett

Lori Phillips

Hollie Benson

Waibhav Tembe

Esteban Braggio

Jeffrey A Kiefer

Christophe Legendre

Richard Posner

Galen H Hostetter

Angela Baker

Jan B Egan

Haiyong Han

Douglas Lake

Edward C Stites

Ramesh K Ramanathan

Rafael Fonseca

A Keith Stewart

Daniel Von Hoff


Peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 24 weeks


Abstract | Full Text

Pancreatic adenocarcinoma (PAC) is among the most lethal malignancies. While research has implicated multiple genes in disease pathogenesis, identification of therapeutic leads has been difficult and the majority of currently available therapies provide only marginal benefit. To address this issue, our goal was to genomically characterize individual PAC patients to understand the range of aberrations that are occurring in each tumor. Because our understanding of PAC tumorigenesis is limited, evaluation of separate cases may reveal aberrations, that are less common but may provide relevant information on the disease, or that may represent viable therapeutic targets for the patient. We used next generation sequencing to assess global somatic events across 3 PAC patients to characterize each patient and to identify potential targets. This study is the first to report whole genome sequencing (WGS) findings in paired tumor/normal samples collected from 3 separate PAC patients. We generated on average 132 billion mappable bases across all patients using WGS, and identified 142 somatic coding events including point mutations, insertion/deletions, and chromosomal copy number variants. We did not identify any significant somatic translocation events. We also performed RNA sequencing on 2 of these patients' tumors for which tumor RNA was available to evaluate expression changes that may be associated with somatic events, and generated over 100 million mapped reads for each patient. We further performed pathway analysis of all sequencing data to identify processes that may be the most heavily impacted from somatic and expression alterations. As expected, the KRAS signaling pathway was the most heavily impacted pathway (P<0.05), along with tumor-stroma interactions and tumor suppressive pathways. While sequencing of more patients is needed, the high resolution genomic and transcriptomic information we have acquired here provides valuable information on the molecular composition of PAC and helps to establish a foundation for improved therapeutic selection.