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

Liang, Winnie S. and Craig, David W. and Carpten, John and Borad, Mitesh J. and Demeure, Michael J. and Weiss, Glen J. and Izatt, Tyler and Sinari, Shripad and Christoforides, Alexis and Aldrich, Jessica and Kurdoglu, Ahmet and Barrett, Michael and Phillips, Lori and Benson, Hollie and Tembe, Waibhav and Braggio, Esteban and Kiefer, Jeffrey A. and Legendre, Christophe and Posner, Richard and Hostetter, Galen H. and Baker, Angela and Egan, Jan B. and Han, Haiyong and Lake, Douglas and Stites, Edward C. and Ramanathan, Ramesh K. and Fonseca, Rafael and Stewart, A. Keith and Von Hoff, Daniel (2012) Genome-wide characterization of pancreatic adenocarcinoma patients using next generation sequencing. PLoS ONE, 7 (10). e43192. ISSN 1932-6203

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Abstract

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.

Item Type:	Article
ID number or DOI:	10.1371/journal.pone.0043192
Keywords:	Pancreatic cancer; cancer treatment; biopsy; RNA; genome analysis; cell fusion; genomic databases
Subjects:	Q Science > QR Microbiology R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
NAU Depositing Author Academic Status:	Faculty/Staff
Department/Unit:	College of Engineering, Forestry, and Natural Science > Biological Sciences
Date Deposited:	16 Oct 2015 20:23
URI:	http://openknowledge.nau.edu/id/eprint/1713

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