Article

Genetic Basis of Pancreas Cancer Development and Progression: Insights from Whole-Exome and Whole-Genome Sequencing

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Clinical Cancer Research (Impact Factor: 8.19). 08/2012; 18(16):4257-65. DOI: 10.1158/1078-0432.CCR-12-0315
Source: PubMed

ABSTRACT Pancreatic cancer is caused by inherited and acquired mutations in specific cancer-associated genes. The discovery of the most common genetic alterations in pancreatic cancer has provided insight into the fundamental pathways that drive the progression from a normal cell to noninvasive precursor lesions and finally to widely metastatic disease. In addition, recent genetic discoveries have created new opportunities to develop gene-based approaches for early detection, personalized treatment, and molecular classification of pancreatic neoplasms.

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    • "In 2013, it is estimated that a total of 45,220 patients will be diagnosed with pancreatic cancer and 38,460 will die of this disease in the United States [1]. Surgical resection through pancreatectomy remains the most viable curative option despite inroads into better understanding of the molecular biology of PDAC [2], emergence of targeted drugs [3] [4], intensity-modulated radiotherapy [5] [6] [7], and neoadjuvant chemotherapy regimen [8] [9]. "
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    • "Pancreatic intraepithelial neoplasia (PanIN) is the most common pancreatic precursor lesion. Activating Kras mutations are almost uniformly present in the early stages of PanIN, whereas subsequent inactivating mutations in p16, p53, and Smad4 occur in advanced lesions [2] [3] [4] [5] [6] [7] [8]. However, because it is difficult to isolate and establish PanIN cell lines from the pancreatic tissue of pancreatic cancer patients, the previous studies of PanIN were mainly conducted using a hybrid of PanIN and pancreatic cancer tissues. "
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