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Title: A preliminary model for the development of sporadic serous ovarian adenocarcinoma

The genetic events that give rise to ovarian adenocarcinoma are poorly understood, nor is it known whether the benign, low malignant potential (LMP) and malignant tumors represent a continuum. This study reports K-ras mutation and loss of heterozygosity (LOH) analysis in 116 tumors, including benign and LMP tumors, on twelve chromosomes chosen mainly because they contain candidate suppressor genes. The data were analyzed with respect to clinicopathological information. The highest rates of LOH were on chromosomes 17 and 18. With the exception of chromosomes 2 and X, all the others were deleted in 25-50% of tumors. Significant associations were found between LOH on chromosomes 7 and 9p, and between chromosomes 5, 17 and 18. LOH was observed in benign and LMP tumors on chromosomes 7 and 9, and homozygous deletions of markers at 9p21 were detected in 2/10 ovarian tumor cell lines. The target of the 9p deletions is likely to be the MTS1/p16 cdk4 inhibitor gene and mutation analysis is under way. A single tumor had a rearrangement of the plasminogen activator inhibitor type 1 locus on chromosome 7 but deletion mapping indicates that this may not be the target of chromosome 7 LOH. K-ras mutations were detected inmore » nine tumors, and were significantly more common in LMP than in malignant tumors. A preliminary genetic model for ovarian tumorigenesis in presented based on these and published data. This model proposes that LMP and malignant tumors arise independently in benign neoplasms in which LOH of chromosomes 7 and 9 has occurred. LMP tumors then develop following activation of the K-ras oncogene, while malignant tumors arise from inactivation of p53 and many other tumor suppressor genes.« less
Authors:
;  [1] ;  [2]
  1. Queensland Institute of Medical Research, Sydney (Australia)
  2. Royal Brisbane Hospital, Sydney (Australia) [and others
Publication Date:
OSTI Identifier:
133483
Report Number(s):
CONF-941009--
Journal ID: AJHGAG; ISSN 0002-9297; TRN: 95:005313-0211
Resource Type:
Journal Article
Resource Relation:
Journal Name: American Journal of Human Genetics; Journal Volume: 55; Journal Issue: Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; GENES; GENE MUTATIONS; OVARIES; NEOPLASMS; HUMAN CHROMOSOMES; GENETIC MAPPING; CHROMOSOMAL ABERRATIONS; PATHOGENESIS; BIOLOGICAL MODELS; BIOLOGICAL MARKERS; GENETICS; STATISTICS; HUMAN CHROMOSOME 17; HUMAN CHROMOSOME 18; TUMOR CELLS; ONCOGENES