Title |
Germline Brca2 Heterozygosity Promotes KrasG12D -Driven Carcinogenesis in a Murine Model of Familial Pancreatic Cancer
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Published in |
Cancer Cell, November 2010
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DOI | 10.1016/j.ccr.2010.10.015 |
Pubmed ID | |
Authors |
Ferdinandos Skoulidis, Liam D. Cassidy, Venkat Pisupati, Jon G. Jonasson, Hordur Bjarnason, Jorunn E. Eyfjord, Florian A. Karreth, Michael Lim, Lorraine M. Barber, Susan A. Clatworthy, Susan E. Davies, Kenneth P. Olive, David A. Tuveson, Ashok R. Venkitaraman |
Abstract |
Inherited heterozygous BRCA2 mutations predispose carriers to tissue-specific cancers, but somatic deletion of the wild-type allele is considered essential for carcinogenesis. We find in a murine model of familial pancreatic cancer that germline heterozygosity for a pathogenic Brca2 truncation suffices to promote pancreatic ductal adenocarcinomas (PDACs) driven by Kras(G12D), irrespective of Trp53 status. Unexpectedly, tumor cells retain a functional Brca2 allele. Correspondingly, three out of four PDACs from patients inheriting BRCA2(999del5) did not exhibit loss-of-heterozygosity (LOH). Three tumors from these patients displaying LOH were acinar carcinomas, which also developed only in mice with biallelic Brca2 inactivation. We suggest a revised model for tumor suppression by BRCA2 with implications for the therapeutic strategy targeting BRCA2 mutant cancer cells. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 4 | 50% |
Canada | 1 | 13% |
Germany | 1 | 13% |
Unknown | 2 | 25% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 4 | 50% |
Scientists | 3 | 38% |
Science communicators (journalists, bloggers, editors) | 1 | 13% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 2 | 2% |
Netherlands | 1 | <1% |
Australia | 1 | <1% |
France | 1 | <1% |
China | 1 | <1% |
United States | 1 | <1% |
Unknown | 112 | 94% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 29 | 24% |
Researcher | 26 | 22% |
Professor > Associate Professor | 13 | 11% |
Student > Postgraduate | 9 | 8% |
Student > Master | 7 | 6% |
Other | 17 | 14% |
Unknown | 18 | 15% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 35 | 29% |
Medicine and Dentistry | 31 | 26% |
Biochemistry, Genetics and Molecular Biology | 27 | 23% |
Unspecified | 2 | 2% |
Business, Management and Accounting | 1 | <1% |
Other | 3 | 3% |
Unknown | 20 | 17% |