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Martin ES , Cesari R , Pentimalli F , Yoder K , Fishel R , Himelstein AL , Martin SE , Godwin AK , Negrini M , Croce CM
The BCSC-1 locus at chromosome 11q23-q24 is a candidate tumor suppressor gene
Proceedings of the National Academy of Sciences of the United States of America. 2003 Sep;100(20) :11517-11522
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Frequent allelic loss at human chromosome 11q23-q24 occurs in a wide variety of cancers, suggesting that this region may harbor a tumor suppressor gene. By constructing a physical map of the LOH11CR2 minimal region of loss on 11q23-q24 associated with lung and breast carcinomas, we were able to clone a hereditary translocation, t(11;12)(q23;q24), in a patient with early-onset breast cancer and family history of cancer. The breakpoint was found within 6 kb of the BCSC-1 candidate tumor suppressor gene located in the LOH11CR2 region whereas additional loss of heterozygosity (LOH) analysis in breast and ovarian tumors, including that of the patient with the t(11;12)(q23;q24), implicated the BCSC-1 locus as the primary target of deletion. Northern analysis of the BCSC-1 mRNA revealed a lack of expression in 33 of 41 (80%) tumor cell lines, and its ectopic expression led to the suppression of colony formation in vitro and tumorigenicity in vivo. These data suggest that BCSC-1 may! exert a tumor suppressor activity and is a likely target of the LOH observed on 11q23-q24 in cancer.
English Article 0027-8424