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

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.

Figure 1

Histology of pancreatic intraepithelial neoplasia (PanIN). The moderate dysplasia present makes this lesion a PanIN-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

Model of the progression from a normal cell to metastatic pancreatic cancer. (Based on an original illustration by Bona Kim).

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).