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Applying next-generation sequencing to pancreatic cancer treatment

Nature Reviews Gastroenterology & Hepatology volume 9, pages 477–486 (2012)Cite this article

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Abstract

Pancreatic cancer is a highly lethal malignancy that presents multiple technical challenges for genomic studies. Next-generation sequencing and its applications have proven successful in the study of other tumour types, unravelling the interplay between DNA and RNA changes that are unique to the tumour. This Review outlines the genomic studies performed to date that have explored the somatic alterations of pancreatic cancer genomes, setting the stage for the introduction of our current technological capabilities. In spite of several challenging aspects posed by pancreatic tumours in particular and clinical sequencing-based diagnostics in general, next-generation sequencing and analysis can now be used in experiments relating to the treatment of patients with this disease. As a means to improve patient outcomes, the application of comprehensive next-generation sequencing and analysis to the genomes of patients with pancreatic cancer to identify therapeutic options is proposed.

Key Points

  • Pancreatic cancer presents multiple challenges to cancer genomic studies, although early studies have defined the predominant mutations in the disease

  • New approaches, based on next-generation sequencing and analysis, might overcome some of these challenges and provide new information about tumour heterogeneity and the full mutational spectrum of each patient's disease

  • Medical interpretation of sequencing data from DNA isolated from pancreatic tumours and matched normal tissue, and RNA isolated from pancreatic tumours, by integrated analysis might identify therapeutic options among small-molecule or antibody-based inhibitors

  • Diagnostic trials that combine next-generation sequencing and medical interpretation of data with the use of targeted therapies should be designed for testing in patients with pancreatic cancer

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Figure 1: The process of exome capture from a whole-genome library.
Figure 2: Data integration between whole genome, exome and transcriptome data from a single cancer case.
Figure 3: A proposed clinical sequencing pipeline.

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Authors and Affiliations

  1. The Genome Institute, Washington University School of Medicine, Campus Box 8501, 4444 Forest Park Avenue, St Louis, 63108, MO, USA

    Elaine R. Mardis

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Mardis, E. Applying next-generation sequencing to pancreatic cancer treatment. Nat Rev Gastroenterol Hepatol 9, 477–486 (2012). https://doi.org/10.1038/nrgastro.2012.126

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