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Review
. 2012 Aug 15;18(16):4257-65.
doi: 10.1158/1078-0432.CCR-12-0315.

Genetic basis of pancreas cancer development and progression: insights from whole-exome and whole-genome sequencing

Christine A Iacobuzio-Donahue  1 , Victor E Velculescu, Christopher L Wolfgang, Ralph H Hruban
Affiliations
Review

Genetic basis of pancreas cancer development and progression: insights from whole-exome and whole-genome sequencing

Christine A Iacobuzio-Donahue et al. Clin Cancer Res. .

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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Conflict of interest statement

Statement of Conflict of Interest: Under a licensing agreement between Johns Hopkins University and Myriad Genetics, Ralph Hruban and Victor E. Velculescu are entitled to a share of royalty payments received by the University on sales of products related to the PALB2 gene. Victor E. Velculescu is a founder of Personal Genome Diagnostics and Inostics, is member of their Scientific Advisory Boards, and owns Personal Genome Diagnostics and Inostics stock, which is subject to certain restrictions under university policy. The terms of these arrangements are managed by Johns Hopkins University in accordance with its conflict-of-interest policies.

Figures

Figure 1
Figure 1
Histology of pancreatic intraepithelial neoplasia (PanIN). The moderate dysplasia present makes this lesion a PanIN-2.
Figure 2
Figure 2
The four most common cystic neoplasms of the pancreas include intraductal papillary mucinous neoplasm (A), mucinous cystic neoplasm with high-grade dysplasia (B), solid-pseudopapillary neoplasm (C), and serous cystadenoma (D).
Figure 3
Figure 3
Model of the progression from a normal cell to metastatic pancreatic cancer. (Based on an original illustration by Bona Kim).
Figure 4
Figure 4
Three scenarios for the clinical application of mutational analyses. A) Sequencing the germline of individuals with a family history. B) Sequencing endoscopically obtained cyst fluid. C) Sequencing the cancer itself. (Based on an original illustration by Bona Kim).
See this image and copyright information in PMC

References

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