SHORT REPORT Somatic mutations in the BRCA1 gene in Chinese sporadic breast and ovarian cancer Ui-Soon Khoo* ,1 , Hilmi Ozcelik 2,3 , Annie NY Cheung 1 , Louis WC Chow 4 , Hextan YS Ngan 5 , Susan J Done 2,3 , ACT Liang 1 , Vivian WY Chan 2 , Gordon KH Au 6 , Wing-Fung Ng 7 , Cycles SP Poon 8 , Yuet-Foon Leung 9 , Florence Loong 1 , Philip Ip 1 , Gavin SW Chan 1 , Irene L Andrulis 2,3,10 , Jing Lu 5 and Faith CS Ho 11 1 Department of Pathology, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong; 2 Department of Pathology and Laboratory Medicine and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto M5G 1X5, Ontario, Canada; 3 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5G 1X5, Ontario, Canada; 4 Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong; 5 Department of Obstetrics and Gynecology, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong; 6 Department of Radiation Therapy and Oncology, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong; 7 Department of Pathology, Ruttonjee Hospital, Hong Kong; 8 Department of Pathology, Pamela Youde Nethersole Hospital, Hong Kong; 9 Pathology Institute, Jockey Club Polyclinic, Sai Ying Pun, Hong Kong; 10 Division of Preventive Oncology, CCO, Toronto, M5G 2L7, Canada; 11 Department of Pathology and Immunology, Monash University, Melbourne, Australia Inherited mutations in the BRCA1 gene confer increased susceptibility to breast and ovarian cancer. Its role in sporadic carcinogenesis is not well de®ned. Somatic mutations in breast cancers have not been reported and to date there are only three reports of somatic mutations in sporadic ovarian cancers. To investigate the contribu- tion of BRCA1 mutations to sporadic breast and ovarian cancer in the Chinese population, we analysed 62 samples from Chinese women using the protein trunca- tion test. There were 40 cases of breast cancer under age 50 and 22 cases of ovarian cancer, all unselected for family history. There was no age selection for the ovarian cancers. We found two somatic BRCA1 mutations in exon 11, one in a breast cancer and the other in an ovarian cancer, both of which result in truncated proteins. Our results indicate that somatic BRCA1 mutations, like somatic mutations in the BRCA2 gene, though very rare, can be found in both breast and ovarian cancers and support a tumor suppressor function for BRCA1 in sporadic tumors. Keywords: BRCA1; somatic mutations; breast cancer; ovarian cancer; Chinese The observed high incidence of loss of heterozygosity in the BRCA1 region in breast and ovarian tumors suggested the presence of somatic mutations in this gene. After the BRCA1 gene was cloned, Futreal et al. (1994) actively attempted to demonstrate this but failed to ®nd any somatic mutations in the 36 breast and 12 ovarian carcinomas they studied which showed LOH at the BRCA1 locus. The ®rst evidence for somatic BRCA1 mutations came from Merajver et al. (1995), who described such mutations in four of their 47 ovarian cases studied. A further somatic mutation in an ovarian cancer was described by Hosking et al. (1995) and a few more have been reported recently by Berchuck et al. (1998). No somatic BRCA1 mutation has ever been reported from breast cancer. Molecular studies of BRCA1 mutations have generally been focused on Caucasian high-risk families (Szabo and King, 1997). The Japanese are the only Asian population in the literature so far. Both Katagiri et al. (1996) and Matsushima et al. (1996) have reported a lower incidence of 3.8 and 5% in their breast and ovarian cancer population respectively. To investigate the contribution of BRCA1 mutations in the Chinese population of Hong Kong, we analysed a series of 40 breast and 22 ovarian cancer tumor samples from Chinese women, all cases being unselected for family history. Sixty-two rapidly frozen fresh tumor specimens were obtained from mastectomy or excision specimens of patients treated for breast carcinoma in Queen Mary Hospital, Tung Wah and Pamela Youde Nethersole Hospitals, Hong Kong; and from excision specimens of patients with ovarian carcinoma in Queen Mary Hospital. Breast cancer cases diagnosed under the age of 50 were selected for this study. Fifteen of the breast cancer patients were between ages 41 ± 50, whereas the remaining 13 and 12 were between the ages 21 ± 35 and 36 ± 40, respectively. There was no age selection for the ovarian cancers which had ages ranging from 25 ± 77 years. The genomic DNA and total RNA were extracted using standard procedures. Non-tumor tissue was also collected whenever available. Informed consent in accord with ethical guidelines was obtained from individuals donating blood specimens for analysis. Prior to extraction, a histological section was cut from all blocks to con®rm the identity of tissues analysed. The entire BRCA1 coding sequence was analysed using the protein truncation test as described previously (Ozcelik et al., 1996). Fresh frozen tumor DNA samples showing truncated products on PTT, as well as DNA extracted from additional tumor and non-tumour samples of these cases were analysed by *Correspondence: U-S Khoo Received 18 November 1998; revised 17 March 1999; accepted 18 March 1999 Oncogene (1999) 18, 4643 ± 4646 ã 1999 Stockton Press All rights reserved 0950 ± 9232/99 $15.00 http://www.stockton-press.co.uk/onc