Loss of markers linked to BRCA1 precedes loss at important cell cycle regulatory genes in epithelial ovarian cancer

John B. Villeneuve, M. Bradley Silverman, Benjamin Alderete, William Arthur Cliby, Hongzhe Li, Gary A. Croghan, Karl C. Podratz, Robert Brian Jenkins

Research output: Contribution to journalArticle

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Abstract

Advanced-stage epithelial ovarian cancers (EOC) from 114 patients were assessed for loss of heterozygosity (LOH or allelic imbalance) at several tumor suppressor gene loci as an initial step in identifying gene alterations important to the development of these tumors. The highest frequency of loss, 84% (86 of 102 cases), was observed for markers mapping near or within BRCA1; other significant frequencies of LOH were observed for loci mapping near or within CDKN2A/CDKN2B (56%), BRCA2 (61%), RB1 (67%), or TP53 (73%). No instance of TP53 LOH was observed without simultaneous allelic imbalance at the BRCA1 region (P = 0.0005). LOH of CDKN2 without loss near the BRCA1 region was seen in only 2 of 75 cases (P < 0.0001), and RB1 LOH without BRCA1 loss occurred in only 1 of 35 tumors (P = 0.0703). These data suggest that LOH of BRCA1, or a closely linked locus, precedes the loss of CDKN2, TP53, and RB1, and imply that inactivation of a tumor suppressor gene in this region is an important early step in the development of these tumors.

Original languageEnglish (US)
Pages (from-to)65-69
Number of pages5
JournalGenes Chromosomes and Cancer
Volume25
Issue number1
DOIs
StatePublished - May 1999

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cdc Genes
Regulator Genes
Allelic Imbalance
Tumor Suppressor Genes
Neoplasms
Loss of Heterozygosity
Genes
Ovarian epithelial cancer

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Loss of markers linked to BRCA1 precedes loss at important cell cycle regulatory genes in epithelial ovarian cancer. / Villeneuve, John B.; Silverman, M. Bradley; Alderete, Benjamin; Cliby, William Arthur; Li, Hongzhe; Croghan, Gary A.; Podratz, Karl C.; Jenkins, Robert Brian.

In: Genes Chromosomes and Cancer, Vol. 25, No. 1, 05.1999, p. 65-69.

Research output: Contribution to journalArticle

Villeneuve, John B. ; Silverman, M. Bradley ; Alderete, Benjamin ; Cliby, William Arthur ; Li, Hongzhe ; Croghan, Gary A. ; Podratz, Karl C. ; Jenkins, Robert Brian. / Loss of markers linked to BRCA1 precedes loss at important cell cycle regulatory genes in epithelial ovarian cancer. In: Genes Chromosomes and Cancer. 1999 ; Vol. 25, No. 1. pp. 65-69.
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