Chromosome 8 genetic analysis and phenotypic characterization of 21 ovarian cancer cell lines.
The short arm of chromosome 8 undergoes frequent loss of heterozygosity (LOH) in ovarian adenocarcinomas. Fine mapping has identified several distinct critical regions within 8p which undergo rates of LOH of 50% or greater, suggesting that there may be more than one tumor suppressor gene located on this chromosome arm. In an effort to refine the location of these putative tumor suppressor genes by homozygosity-mapping-of-deletion analysis, we have analyzed 21 ovarian cancer cell lines with 19 polymorphic microsatellite markers from 8p. Eleven of the cell lines (55%) were homozygous at every marker, indicating loss of an entire 8p arm. No smaller extended regions of hemizygosity were identified. Refinement of these 8p target regions was therefore not possible, but this analysis did identify the ovarian cancer cell lines that would be most appropriate for microcell-mediated chromosome transfer to complement the hypothesized mutation in the target tumor suppressor gene(s) on 8p. The 11 cell lines that had undergone 8p LOH were therefore characterized for colony formation in soft agar and tumor formation in nude mice. We identified four cell lines (JAM, OVCA4, OVCA5, and OVCA8) that were hemizygous for 8p and that formed colonies in soft agar and tumors in nude mice, making them ideal cell lines for chromosome 8 or candidate gene transfer.
Arnold
Jeremy M
JM
The Queensland Institute of Medical Research, Queensland 4029, Hernston, Australia. jeremyA@qimr.edu.au
Woollatt
Erica
E
Chenevix-Trench
Georgia
G
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D051379:Mice; D008819:Mice, Nude; D018895:Microsatellite Repeats; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D014407:Tumor Cells, Cultured / Q000648:ultrastructure