DBC2, a candidate for a tumor suppressor gene involved in breast cancer
Masaaki Hamaguchi *, Jennifer L. Meth *, Christine von Klitzing *, Wen Wei *, Diane Esposito *, Linda Rodgers *, Tom Walsh , Piri Welcsh , Mary-Claire King , and Michael H. Wigler *
*Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724; and Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA 98195-7720
Contributed by Michael H. Wigler, August 26, 2002
A previously uncharacterized gene, DBC2 (deleted in breast cancer), was cloned from a homozygously deleted region at human chromosome 8p21. DBC2 contains a highly conserved RAS domain and two putative protein interacting domains. Our analyses indicate that DBC2 is the best candidate tumor suppressor gene from this region. It lies within the epicenter of the deletions and is homozygously deleted in 3.5% (7/200) of breast tumors. Mutation analysis of DBC2 led to discovery of two instances of somatic missense mutations in breast tumor specimens, whereas no missense mutations were found in other candidates from the region. Unlike other genes in the region, expression of DBC2 is often extinguished in breast cancer cells or tissues. Moreover, our functional analysis revealed that DBC2 expression in breast cancer cells lacking DBC2 transcripts causes growth inhibition. By contrast, expression of a somatic mutant discovered in a breast cancer specimen does not suppress the growth of breast cancer cells.
To whom correspondence should be addressed.
E-mail: hamaguch@cshl.edu.
www.pnas.org/cgi/doi/10.1073/pnas.212516099 |
