| First Author | Skoulidis F | Year | 2010 |
| Journal | Cancer Cell | Volume | 18 |
| Issue | 5 | Pages | 499-509 |
| PubMed ID | 21056012 | Mgi Jnum | J:166678 |
| Mgi Id | MGI:4849308 | Doi | 10.1016/j.ccr.2010.10.015 |
| Citation | Skoulidis F, et al. (2010) Germline Brca2 heterozygosity promotes Kras(G12D) -driven carcinogenesis in a murine model of familial pancreatic cancer. Cancer Cell 18(5):499-509 |
| abstractText | 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. |
