Whole genome sequencing defines the genetic heterogeneity of familial pancreatic cancer

Roberts, N. J., Norris, A. L., Petersen, G. M., Bondy, M. L., Brand, R., Gallinger, S., Kurtz, R. C., Olson, S. H., Rustgi, A. K., Schwartz, A. G., Stoffel, E. M., Syngal, S., Zogopoulos, G., Ali, S. Z., Axilbund, J., Chaffee, K. G., Chen, Y. C., Cote, M. L., Childs, E. J., Douville, C., Goes, F. S., Herman, J. M., Iacobuzio-Donahue, C., Kramer, M., Makohon-Moore, A., McCombie, R. W., McMahon, K. W., Niknafs, N., Parla, J., Pirooznia, M., Potash, J. B., Rhim, A. D., Smith, A. L., Wang, Y., Wolfgang, C. L., Wood, L. D., Zandi, P. P., Goggins, M., Karchin, R., Eshleman, J. R., Papadopoulos, N., Kinzler, K. W., Vogelstein, B., Hruban, R. H., Klein, A. P. (2016) Whole genome sequencing defines the genetic heterogeneity of familial pancreatic cancer. Cancer Discov, 6 (2). pp. 166-175. ISSN 2159-8290 (Electronic)2159-8274 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/26658419
DOI: 10.1158/2159-8290.cd-15-0402

Abstract

Pancreatic cancer is projected to become the second leading cause of cancer-related death in the United States by 2020. A familial aggregation of pancreatic cancer has been established, but the cause of this aggregation in most families is unknown. To determine the genetic basis of susceptibility in these families, we sequenced the germline genome of 638 familial pancreatic cancer patients. We also sequenced the exomes of 39 familial pancreatic adenocarcinomas. Our analyses support the role of previously identified familial pancreatic cancer susceptibility genes such as BRCA2, CDKN2A and ATM, and identify novel candidate genes harboring rare, deleterious germline variants for further characterization. We also show how somatic point mutations that occur during hematopoiesis can affect the interpretation of genome-wide studies of hereditary traits. Our observations have important implications for the etiology of pancreatic cancer and for the identification of susceptibility genes in other common cancer types.

Item Type: Paper
Subjects: diseases & disorders > cancer > cancer types > pancreatic cancer
Investigative techniques and equipment > assays > whole genome sequencing
CSHL Authors:
Communities: CSHL labs > McCombie lab
Stanley Institute for Cognitive Genomics
Depositing User: Matt Covey
Date Deposited: 17 Feb 2016 21:26
Last Modified: 17 Feb 2016 21:26
PMCID: PMC4744563
Related URLs:
URI: http://repository.cshl.edu/id/eprint/32362

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