The BCSC-1 locus at chromosome 11q23-q24 is a candidate tumor suppressor gene

Eric S. Martin, Rossano Cesari, Francesca Pentimalli, Kristine Yoder, Richard Fishel, Andrew L. Himelstein, S. Eric Martin, Andrew K. Godwin, Massimo Negrini, Carlo M. Croce

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)11517-11522
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number20
DOIs
Publication statusPublished - Sep 30 2003

ASJC Scopus subject areas

  • Genetics
  • General

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