Details

Autor(en) / Beteiligte

• Skoulidis, Ferdinandos
• Cassidy, Liam D
• Pisupati, Venkat
• Jonasson, Jon G
• Bjarnason, Hordur
• Eyfjord, Jorunn E
• Karreth, Florian A
• Lim, Michael
• Barber, Lorraine M
• Clatworthy, Susan A
• Davies, Susan E
• Olive, Kenneth P
• Tuveson, David A
• Venkitaraman, Ashok R

Titel

Germline Brca2 heterozygosity promotes Kras(G12D) -driven carcinogenesis in a murine model of familial pancreatic cancer

Ist Teil von

• Cancer cell, 2010-11, Vol.18 (5), p.499

Ort / Verlag

United States

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.