DBC2, a Candidate for a Tumor Suppressor Gene Involved in Breast Cancer

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...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 99; no. 21; pp. 13647 - 13652
Main Authors Hamaguchi, Masaaki, Meth, Jennifer L., von Klitzing, Christine, Wei, Wen, Esposito, Diane, Rodgers, Linda, Walsh, Tom, Welcsh, Piri, King, Mary-Claire, Wigler, Michael H.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 15.10.2002
National Acad Sciences
The National Academy of Sciences
Subjects
Base Sequence
Biological Sciences
Breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Cell Division - genetics
Cell lines
Chromosome Mapping
Chromosomes, Human, Pair 8 - genetics
Cloning, Molecular
DNA Mutational Analysis
DNA, Neoplasm - genetics
Female
Gene Deletion
Gene Expression
Genes
Genes, Tumor Suppressor
Genetic mutation
Genetics
HeLa cells
Homozygote
Humans
Molecular Sequence Data
Mutation, Missense
Phylogeny
Polymerase chain reaction
Proteins
Tumor cell line
Tumor Cells, Cultured
Tumor suppressor genes
Tumors
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Summary: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.
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To whom correspondence should be addressed. E-mail: hamaguch@cshl.edu.
Contributed by Michael H. Wigler
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.212516099