Allele loss from large regions of chromosome 17 is common only in certain histological subtypes of ovarian carcinomas

Abstract

Summary Using a panel of ten polymorphic markers, we examined the frequency of loss of heterozygosity (LOH) on chromosome 17 in 55 sporadic ovarian tumours. LOH on 17p and 17q was observed to be 50% and 62% respectively. LOH at D17S5 was detected in 24/36 (67%) of malignant cases and in 19/43 (44%) at TP53; the marker D17S855 intragenic to the BRCAJ gene showed allele loss in 50% (20/40) cases. The data presented here suggest that loss of the whole chromosome 17 is a relatively frequent event (30%) in ovarian carcinomas and this observation is especially frequent for serous, transitional cell and anaplastic histological subtypes. Mucinous and endometrioid ovarian tumours showed only short interstitial deletions (4/11, 36%). The overall frequency of the short deletions was relatively low (7/43, 16%) in our panel of carcinomas. Amplification of c-erbB-2/neu oncogene was detected in 32% (11/34) of the carcinomas tested; the gene was amplified only in those histological subtypes in which high incidence of LOH on chromosome 17 was observed, and was associated with advanced stages of the disease. We conclude that different histological types of tumour may have different aetiological mechanisms, and tumour-suppressor genes on chromosome 17 might be associated specifically with serous and transitional cell ovarian carcinomas.

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

“…While Pierretti et al (1995) reported an overall di erence in LOH of 17p versus 17q markers in endometrioid and mucinous tumors, the LOH patterns displayed by each tumor type was not described and therefore comparisons with the present study cannot be made. The observation by Papp et al (1996) that LOH across multiple chromosome 17q alleles is infrequent in tumors of endometrioid, mucinous and clear cell histology are comparable with those described in the present study. However, LOH patterns observed for the endometrioid and mucinous tumors di ered.…”

“…In addition, the frequent LOH of TP53 accompanying LOH of all informative 17q loci suggests that complete loss of an entire chromosome 17 homolog is a frequent event in epithelial ovarian cancer. The high frequency of LOH of 17q loci is in line with the independent reports demonstrating a frequent LOH (ranging from 30 to 89%) of all polymorphic markers on chromosome 17 (Foulkes et al, 1993;Tavassoli et al, 1993;Pieretti et al, 1995;Papp et al, 1996).…”

“…The rarity of interstitial loss of chromosome 17 loci observed in the present study contributes to the growing body of literature demonstrating that reduction to homozygosity is a common occurrence in the serous histologic type of ovarian tumors (Foulkes et al, 1993;Pierretti et al, 1995;Papp et al, 1996). Pierreti et al (1995) postulated that the loss of an entire chromosome 17 homolog in serous tumors confers a selective advantage during progression such that this event would bring about the development of a highly malignant tumor.…”

“…As the loss of alleles suggest the presence of tumor suppressors implicated in ovarian carcinogenesis, the accurate de®nition of such regions of LOH will aid in the isolation of genes involved in ovarian tumorigenesis. However, in ovarian cancer a signi®cant proportion of tumors display loss of all informative polymorphic loci, strongly suggestive of a loss of an entire chromosome 17 homolog (Foulkes et al, 1993;Tavassoli et al, 1993;Pierretti et al, 1995;Papp et al, 1996). This conclusion is supported by a recent cytogenetic survey showing the frequent occurrence of reduction to monosomy (due to non-dysjunction, with or without duplication), and the uncommon occurrence of translocations, deletions and isochromosomes in ovarian tumors (Mertens et al, 1997).…”

“…Increased expression of HER2/neu accompanied with or without gene ampli®cation is also a feature of some tumors of high grade and late stage (Slamon et al, 1989). Recently, HER2/neu gene ampli®cations has been found to occur only in the subset of ovarian tumors which display LOH of a number of chromosome 17 loci (Papp et al, 1996). In some studies, an increased expression of NME1 has been associated with a more aggressive phenotype (Leary et al, 1995;Mandai et al, 1995;Schneider et al, 1996), although this association remains controversial (Harlozinska et al, 1996).…”