Genetic instability in human ovarian cancer cell lines.

Abstract

We have analyzed the stability of microsatellites in cell lines derived from human ovarian cancers and found that 5 out of 10 of the ovarian tumor cell lines are genetically unstable at the majority of the loci analyzed. In clones and subclones derived serially from one of these cell lines (2774; serous cystadenocarcinoma), a very high proportion of microsatellites distributed in many different regions of the genome change their size in a mercurial fashion. We conclude that genomic instability in ovarian tumors is a dynamic and ongoing process whose high frequency may have been previously underestimated by PCR-based wild-type alleles of the human MSH2 gene. However the wild-type allele was lost at some point early during tumorigenesis so that DNA isolated either from the patient's ovarian tumor or from the 2774 cell line carries only the mutant allele of the human MSH2 gene. The genetic instability observed in the tumor and cell line DNA, together with the germ-line mutation in a mismatch-repair gene, suggest that the MSH2 gene is involved in the onset and/or progression in a subset of ovarian cancer.

Loss of heterozygosity for defined regions on chromosomes 3, 11 and 17 in carcinomas of the uterine cervix

“…One tumour in our series meets these criteria. RER is often found in colorectal cancers, colon, endometrial (Burks et al, 1994) and ovarian cancers (Orth et al, 1994;Liu et al, 1995). In cervical cancer, two groups (Mitra et al, 1995;Larson et al, 1996) reported microsatellite instability.…”

An optimum anti-melanoma response in mice immunized with fibroblasts transfected with DNA from mouse melanoma cells requires the expression of both syngeneic and allogeneic MHC-determinants

“…Genetic instability is a characteristic phenotype of cancer cells. [14][15][16][17][18] Under most circumstances, however, TAAs expressed by malignant cells are insufficiently immunogenic. Effective immune responses that can result in rejection of the …”

Searching for microsatellite mutations in coding regions in lung, breast, ovarian and colorectal cancers

“…Somatically acquired microsatellite alterations occur frequently in endometrial, gastrointestinal, testicular, colorectal and ovarian carcinomas leading to characterizing these tumors as microsatellite instable (MSI+) or not (MSI7) (Gurin et al, 1999;King et al, 1997;Liu et al, 1995;Orth et al, 1994;Yamamoto et al, 1997). These alterations are correlated with mutations in mismatch repair (MMR) system genes (hMSH2, hMLH1, hMSH6 etc.)…”