Localization of a putative liver tumor suppressor locus to a 950-kb region of human 11p11.2-p12 using rat liver tumor microcell hybrid cell lines.
We previously demonstrated that a locus (or loci) linked to the D11S436 marker, which is within the approximately 6-Mb cen-p12 region of human chromosome 11, suppresses the tumorigenic potential of some rat liver epithelial tumor microcell hybrid (MCH) cell lines. To more precisely map this putative liver tumor suppressor locus, we examined 25 loci from human chromosome 11 in suppressed MCH cell lines. Detailed analysis of these markers revealed a minimal area of overlap among the suppressed MCH cell lines corresponding to the chromosomal region bounded by (but not including) microsatellite markers D11S1319 and D11S1958E and containing microsatellite markers D11S436, D11S554, and D11S1344. Direct examination of the kang ai 1 (KA/1) prostatic adenocarcinoma metastasis suppressor gene (which is closely linked to D11S1344) produced evidence suggesting that this locus was not responsible for tumor suppression in this model system. In addition, our data strongly suggested that the putative liver tumor suppressor locus was distinct from other known 11p tumor suppressor loci, including the multiple exotoses 2 locus (at 11p11.2-p12), Wilms' tumor 1 locus (at 11p13), and Wilms' tumor 2 locus (at 11p15.5). The results of this study significantly narrowed the chromosomal location of the putative liver tumor suppressor locus to a region of human 11p11.2-p12 that is approximately 950 kb. This advance forms the basis for positional cloning of candidate genes from this region and, in addition, identified a number of chromosomal markers that will be useful for determining the involvement of this locus in the pathogenesis of human liver cancer.
Coleman
W B
WB
Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill 27599, USA.
Esch
G L
GL
Borchert
K M
KM
McCullough
K D
KD
Reid
L H
LH
Weissman
B E
BE
Smith
G J
GJ
Grisham
J W
JW
D000818:Animals; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D016147:Genes, Tumor Suppressor; D016162:Genes, Wilms Tumor; D006801:Humans; D006822:Hybrid Cells; D008114:Liver Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D018895:Microsatellite Repeats; D016133:Polymerase Chain Reaction; D051381:Rats; D014407:Tumor Cells, Cultured