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Genomic Alterations in Sporadic Pancreatic Cancer

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Molecular Genetics of Pancreatic Cancer

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Abstract

The prognosis for most patients afflicted by pancreatic cancer still remains dismal. With the majority of cases being diagnosed at advanced stages, only minimal improvements in survival rates have been achieved using current therapeutic approaches. Nonetheless, remarkable research efforts over the past decade have enabled a detailed understanding of the molecular mechanisms underlying the pathogenesis of pancreatic cancer. According to the current state of knowledge, pancreatic carcinogenesis is a multistep process that requires alterations in a compendium of oncogenes, tumor-suppressor genes and genome-maintenance genes. The most frequent aberrations (somatic point mutations and allelic losses) affect oncogenes (KRAS2) and tumor-suppressor genes (CDKN2A/p16, TP53, SMAD4/DPC4) that have a key role in transcription, proliferation and regulation of the cell cycle, amongst others. In addition to these known mutational “mountains,” a wide number of less frequently altered genes (“hills”) have been discovered, which play an important part in defining the unique biology and behavior of each individual pancreatic cancer. A deeper understanding of the genetic landscape of pancreatic cancer, enhanced by “next-generation” high-throughput technologies will hopefully promote the development of new methods for early diagnosis and facilitate improvements in current therapeutic approaches.

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  1. The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, CRB II Room 345, 1550 Orleans Street, Baltimore, MD, 21231, USA

    Marco Dal Molin M.D. & Anirban Maitra M.B.B.S.

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    Anirban Maitra

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Molin, M.D., Maitra, A. (2013). Genomic Alterations in Sporadic Pancreatic Cancer. In: Simeone, D., Maitra, A. (eds) Molecular Genetics of Pancreatic Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6549-2_1

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