Journal Article

Localization of a Tumor Suppressor Gene in 11p15.5 Using the G401 Wilms' Tumor Assay

Laura Hink Reid, Ande West, Daniel G. Gioeli, Karen K. Phillips, Kevin F. Kelleher, Diana Araujo, Eric J. Stanbridge, Steven F. Dowdy, Daniela S. Gerhard and Bernard E. Weissman

in Human Molecular Genetics

Volume 5, issue 2, pages 239-247
Published in print February 1996 | ISSN: 0964-6906
Published online February 1996 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/5.2.239
Localization of a Tumor Suppressor Gene in 11p15.5 Using the G401 Wilms' Tumor Assay

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Multiple studies have underscored the importance of loss of tumor suppressor genes in the development of human cancer. To identify these genes, we used somatic cell hybrids in a functional assay for tumor suppression in vivo. A tumor suppressor gene in 11p15.5 was detected by transferring single human chromosomes into the G401 Wilms' tumor cell line. In order to better map this gene, we created a series of radiationreduced t(X;11) chromosomes and characterized them at 24 loci between H-RAS and β-globin. Interestingly, three of the chromosomes were indistinguishable as determined by genomic and cytogenetic analyses. Each contains an interstitial deletion with one breakpoint in 11p14.1 and the other breakpoint between the D11S601 and D11S648 loci in 11p15.5. PFGE analysis localized the 11p15.5 breakpoints to a 175 kb MluI fragment that hybridized to D11S601 and D11S648 probes. Genomic fragments from this 175 kb region were hybridized to DNA from mouse hybrid lines containing the Δt(X;11) chromosomes. This analysis detected the identical 11p15.5 breakpoint which disrupts a 7.8 kb EcoRI fragment in all three of the Δt(X;11) chromosomes, suggesting they are subclones of the same parent colony. Upon transfer into G401 cells, one of the chromosomes suppressed tumor formation in nude mice, while the other two chromosomes lacked this ability. Thus, our mapping data indicate that the gene in 11p15.5 which suppresses tumor formation in G401 cells must lie telomeric to the D11S601 locus. Koi et al. (Science 260: 361–364, 1993) have used a similar functional assay to localize a growth suppressor gene for the RD cell line centromeric to the D11S724 locus. The combination of functional studies by our lab and theirs significantly narrows the location of the tumor suppressor gene in 11p15.5 to the ∼500 kb region between D11S601 and D11S724.

Journal Article.  6520 words.  Illustrated.

Subjects: Genetics and Genomics

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