Somatic genetic alterations (LOH) in benign, borderline and invasive ovarian tumours: Intratumoral molecular heterogeneity

Loss of heterozygosity (LOH) affects a number of chromosome regions in ovar ian cancer, pointing to the possible involvement of tumour-suppressor genes in ovarian tumorigenesis. We performed comparative analysis of allelic los s at 6 frequently affected chromosome regions in a panel of 53 benign, bord erline and malignant ovarian tumours. Precursor lesions could provide evide nce that an accumulation of genetic events is required for normal ovarian e pithelium to generate malignant tumours. LOH on chromosome Ip was relativel y common in benign, borderline and malignant tumours, while at 11p and 7q i t was observed not only in invasive but also in borderline tumours. Moreove r, 17q and 18q were affected mainly in advanced malignant tumours and revea led a high frequency of clonal intratumoral heterogeneity. We encountered d ifferent spectra of genetic alterations in primary tumours and their metast asis, which may be the results of intratumoral heterogeneity leading to dis semination in only some sub-clones. (C) 1999 Wiley-Liss, Inc.