Characterization of Chromosome 9 in Human Ovarian Neoplasia Identifies Frequent Genetic Imbalance on 9q and Rare Alterations Involving 9p, Including CDKN2

David C. Schultz, Lisa Vanderveer, Robert F. Ozols, Thomas C. Hamilton, Andrew K. Godwin, Kenneth H. Buetow, Matthew P. Boente

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

We have examined 41 forms of ovarian cancer for genetic alterations on chromosome 9 using a combination of five RFLP DNA probes and 15 simple tandem repeat polymorphisms. Genetic imbalance (i.e., loss of heterozygosity, microsatellite instability, amplification) for 1 or more informative markers on chromosome 9 was observed in 66% (27 of 41) of our tumor panel. Genetic imbalance was observed on 9q in 59% (24 of 41) of tumors informative for at least one locus. In contrast, only 13% (5 of 40) of informative tumors demonstrated a genetic alteration involving 9p. Furthermore, allelic loss on 9q was more common in late stage tumors (63%, 17 of 27) and poorly differentiated tumors (75%, 15 of 20) as compared to benign and early stage tumors (30%, 3 of 10). Evaluation of 15 tumors showing limited regions of genetic imbalance has identified 2 candidate tumor suppressor regions on 9q and 1 on 9p. Interestingly, the regions defined to 9p21-p24,9q31, and 9q32-q34 all overlap with several known disease loci. In this aspect, the potential role of the CDKN2 gene at 9p21-p22 in ovarian carcinogenesis was assessed in an extended panel of ovarian tumors, 11 human ovarian carcinoma cell lines, and 1 cervical tumor cell line. With the use of comparative multiplex PCR, homozygous deletions were detected in 16 of 115 (14%) fresh tumors and 3 of 12 cancer cell lines. For those tumors demonstrating allelic loss for markers on 9p no somatic mutations were observed in the retained allele of CDKN2, as determined by single-strand conformation polymorphism analysis, but a mutation was observed in an additional cell line. Furthermore, CDKN2 mRNA levels were similar in the 9 cancer cell lines that retain CDKN2, as compared to normal human ovarian surface epithelial cell lines. Overall, our results suggest the potential involvement of a gene or genes on chromosome 9q and de-emphasize a significant role for the CDKN2 gene on 9p in the initiation and progression of ovarian cancer.

Original languageEnglish (US)
Pages (from-to)2150-2157
Number of pages8
JournalCancer Research
Volume55
Issue number10
StatePublished - May 15 1995
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Schultz, D. C., Vanderveer, L., Ozols, R. F., Hamilton, T. C., Godwin, A. K., Buetow, K. H., & Boente, M. P. (1995). Characterization of Chromosome 9 in Human Ovarian Neoplasia Identifies Frequent Genetic Imbalance on 9q and Rare Alterations Involving 9p, Including CDKN2. Cancer Research, 55(10), 2150-2157.