Overexpression of the p53 protein and allele loss at 17p13 in ovarian carcinoma

Abstract

Mouse monoclonal antibodies PAb 240 and PAb 1801 which specifically immunoprecipitate p53 protein, were used to examine 27 fresh ovarian tumours (16 serous adenocarcinomas, six endometrioid carcinomas, one mucinous adenocarcinoma, one mucinous borderline tumour and three benign adenomas). Eleven out of 16 (69%) serous adenocarcinomas and one endometrioid tumour showed positive staining with one or both antibodies and none of the mucinous or benign tumours stained with either antibody. DNA from tumour and peripheral blood leukocytes was used to identify allelic deletions on chromosome 17p in tumours. 11/12 positively staining tumours showed less of heterozygosity (LOH) on 17p at the nearest informative locus to the p53 gene. In this series of ovarian tumours, LOH on 17p correlates closely with the aberrant expression of the p53 protein in a high proportion of advanced stage serous adenocarcinomas. This observation suggests that the p53 tumour suppressor gene is involved in the evolution of epithelial ovarian cancer (EOC) and may have prognostic significance. Images Figure 2 Figure 3

Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma

“…[4][5][6] Throughout chromosome 17 frequent genetic deletions have been identified, suggesting that multiple tumour-suppressor genes may exist on this chromosome. [26][27][28][29] Our data therefore implicate miR-195 and miR-497 as potential tumour-suppressor genes. Since its first description by Swerdlow in 1959, primary peritoneal carcinoma has been treated similarly to ovarian serous carcinoma by surgery and chemotherapy.…”

Allelotyping defines minimal imbalance at chromosomal region 17q25 in non-serous epithelial ovarian cancers

“…These genes include the TP53 tumor suppressor at 17p13 (Marks et al, 1991;Okamoto et al, 1991;Tsao et al, 1991;Eccles et al, 1992;Milner et al, 1993), the HER2/neu oncogene at 17q12 (Slamon et al, 1989), the BRCA1 breast-ovarian cancer susceptibility gene at 17q12 (Miki et al, 1994;Merajver et al, 1995), and the NME1 tumor metastasis marker on 17q21-23 (Viel et al, 1995;Scambia et al, 1996;Schneider et al, 1996). Somatic mutations and increased expression of TP53 have been more often reported in high grade and later stage tumors (Berchuck et al, 1994;Kupryjanczyk et al, 1993).…”

Patterns of expression of chromosome 17 genes in primary cultures of normal ovarian surface epithelia and epithelial ovarian cancer cell lines

“…The TP53 tumor-suppressor gene (TSG) at 17p13.1 is one of the most frequently mutated genes in EOC (Okamoto et al, 1991). However, LOH analysis suggests the location of novel TSGs on the short arm of chromosome 17 at or close to the TP53 locus (Okamoto et al, 1991;Tsao et al, 1991;Eccles et al, 1992;Cliby et al, 1993;Foulkes et al, 1993;Yang-Feng et al, 1993) and at a more telomeric region, 17p13.3 (Phillips et al, 1993;Konishi et al, 1998;Phelan et al, 1998;Hoff et al, 2000). A number of genes on the long arm of chromosome 17 also have been shown to be implicated in EOC: the ERBB2 oncogene at 17q21.1 (Slamon et al, 1989), the hereditary breast/ ovarian cancer TSG BRCA1 at 17q21.1 (Miki et al, 1994;Merajver et al, 1995) and the NME1 tumor metastasis marker gene at 17q21.3 (Mandai et al, 1994;Leary et al, 1995;Schneider et al, 1996Schneider et al, , 2000.…”