Frequent occurrence of loss of heterozygosity among tumor suppressor genesin uterine leiomyosarcoma

Objective. Leiomyosarcoma of the uterus is a rare smooth muscle tumor; it i s extremely malignant and the rates of local recurrence and metastasis are high. Since tumor suppressor genes are commonly altered in malignant tumors , it is possible that mutations in such genes are involved in the developme nt of uterine leiomyosarcoma. Methods. Fifty-five patients (37-70 years of age) diagnosed as having smoot h muscle tumors of the uterus were selected. DNA was extracted from four or five 8-mu m-thick consecutive tissue sections of each smooth muscle tumor from the paraffin-embedded blocks. Loss of heterozygosity (LOH) was investi gated at nine loci within or close to tumor suppressor genes (TP53, RB1, DC C, NM23, WT1, D14S267, P16, DPC4, PTCH). Results. Nineteen of twenty leiomyosarcomas revealed at least one instance of LOH among eight of the nine markers tested (one locus showed no LOH at a ll). In fact, 11 of the 20 cases exhibited two or more instances of LOH and , of the remaining 9 cases, 4 showed a point mutation of p53 in addition to an alteration in one of the 9 markers, while one exhibited a p53 mutation only. Conclusion. An accumulation of genetic alterations among tumor suppressor g enes may play a key role in the tumorigenesis and progression of uterine le iomyosarcoma. (C) 1999 Academic Press.