Model of genetic progression in ovarian cancer with comparative genomic hybridization
- Univ. of California, San Francisco, CA (United States); and others
We have performed comparative genomic hybridization (CGH) and analysis of loss of heterozygosity (LOH) using DNA obtained from 44 common epithelial ovarian tumors (benign 8, borderline 3, low grade 11, high grade 22) with the goal of developing a model for genetic progression in common epithelial ovarian cancer. Five general features are apparent from these studies: (1) There is a high concordance (0.85) between LOH and reduced copy number measured by CGH suggesting that most LOH is caused by physical deletion. (2) The total number of aberrations/tumor increased with histologic grade (Kurskal-Wallis, p<0.01). (3) Gene dosage abnormalities 17p-, 17q- and 3q+ occur at highest frequency, f, (f>0.3) and in both low grade and high grade tumors; abnormalities 9q-, 22q-, and Xp- occur at intermediate frequencies (0.2<0.3) and only in malignant tumors while abnormalities 6p+, 8p- and 8q+ occur at lower frequency (f<0.2) and only in high grade tumors. (4) Tumors with one or more of the frequent early or cancer specific aberrations usually carry many more aberrations per tumor (>15/tumor) than tumors that do not (<5/tumor). (5) Many of the genetic abnormalities are correlated. Specifically, strong correlations (Fischer, p<0.01) were observed for the aberration pairs: 16q-:8p-; 17q-:9q; 8p-:8q+; 17p-:17q-; 22q-:9q-; Xp-:9q; 3q+:6p+; and 3q+:Xp-. Taken together, these observations suggest a parallel pathway model for genetic progression in which 17p-, 17q- and 3q+ are independent initial genetic events; 9q-, 22q- and Xp- are intermediate events and 6p+, 8p- and 8q+ are late events.
- OSTI ID:
- 133522
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0250
- 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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