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Mutations in the BRCA2 Gene in Hepatocellular Carcinomas¹

Department of Human Genome Analysis, The Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 1-37-1 Kami-ikebukuro, Toshimaku, Tokyo 170 [T. K., Y. M.], and Laboratory of Molecular Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minatoku, Tokyo 108 [Y. N.], Japan

To investigate whether the BRCA2 gene plays a role in carcinogenesis of hepatocellular carcinomas or pancreatic cancers in view of frequent losses of heterozygosity on chromosome 13q12-13 in those tumors, we screened the entire coding region of this gene for mutations in 60 hepatocellular carcinomas and 36 pancreatic cancers. No alteration was found in any of the pancreatic cancers examined, but three mutations were identified in hepatocellular carcinomas; one was a 6-bp somatic deletion within intron 6. The other two mutations we identified in hepatocellular carcinomas were missense mutations in the germ line, although all BRCA2 mutations thus far detected in patients with familial breast cancers likewise have been deletions. None of 194 other patients with cancers or 44 normal controls exhibited either mutation. Combined with our demonstration of BRCA2 expression in adult liver tissue, the evidence implies that inactivation of BRCA2 may play some role in development or progression of hepatocellular carcinoma and might predispose carriers of mutant alleles to liver malignancies.

¹ This work was supported in part by a special grant for Strategic Advanced Research on Cancer from the Ministry of Education, Culture, Sports and Science of Japan and by a grant from the Japanese Ministry of Health and Welfare.

² To whom requests for reprints should be addressed. Phone/Fax: 81-3-5394-3926; E-mail: tkatagi@hgc.ims.u-tokyo.ac.jp.

Received 5/24/96. Accepted 8/26/96.

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