Loss of heterozygosity at E-cadherin and other loci on chromosome 16 in ovarian cancer
- Yale Univ. School of Medicine, New Haven, CT (United States); and others
Our study of genome-wide screening and mapping of genetic aberrations by comparative genomic hybridization (CGH) revealed that the copy number of DNA sequences on chromosome 16q was reduced in a significant number of ovarian tumors. Loss of heterozygosity (LOH) on 16q has only been reported in ovarian tumors from the Japanese population; this arm has not been thoroughly studied in most LOH analyses of ovarian cancers. We have investigated LOH status at four chromosome 16q loci in 74 common epithelial ovarian tumors (benign and borderline 16, grade I 5, GII 6 and GIII 47). LOH frequencies of .27 (9/33), .19 (10/54), .23 (8/35) and .24 (10/42) were found at HP, D16S408, D16S421 and E-cadherin (E-cad) loci, respectively. Considering overall LOH on chromosome 16q, 26 out of 62 cases (41.9%) heterozygous for one or more loci showed LOH at a minimum of one locus. Our results are consistent with the observation made by CGH and also imply that most LOH in 16q is associated with physical deletion of at least a portion of 16q. E-cad is an intercellular adhesion molecule of epithelial tissues, and reduced E-cad expression is associated with invasiveness of several cancers (breast, bladder, lung, etc.). Thus E-cad may function as a tumor suppressor gene. In addition, the cell matrix adhesion regulator gene (CMAR), which is located distal to E-cad, may be a second candidate. This possibility is currently being investigated by additional LOH analysis. Southern analysis of DNA from tumors with LOH using a full-length E-cad cDNA probe detected only Pvull and MspI polymorphisms but no gross alterations in the remaining alleles. Further studies by SSCP, which explore the possible inactivating mutations in the remaining E-cad alleles, are in progress.
- OSTI ID:
- 133512
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0240
- Journal Information:
- American Journal of Human Genetics, Vol. 55, 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
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