Human Molecular Genetics, Vol 5, 239-247, Copyright © 1996 by Oxford University Press
LH Reid, A West, DG Gioeli, KK Phillips, KF Kelleher, D Araujo, EJ Stanbridge, SF Dowdy, DS Gerhard and BE Weissman
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 radiation-reduced
t(X;11) chromosomes and characterized them at 24 loci between H-RAS and
beta-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 delta t(X;11)
chromosomes. This analysis detected the identical 11p15.5 breakpoint which
disrupts a 7.8 kb EcoRI fragment in all three of the delta t(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 approximately 500 kb region between D11S601 and D11S724.
ARTICLES
Localization of a tumor suppressor gene in 11p15.5 using the G401 Wilms' tumor assay
Department of Pathology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599, USA.
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