Abstract
Backgroud: Leiomyosarcoma (LMS) is characterized by malignant smooth muscle cells. LMS are principally tumours of adult life, children rarely develop these tumours. The cause of LMS is not understood, however the genetic alterations are thought to be important, if not inciting, in the formation and progression of sarcoma. The silencing of tumour suppressor genes by promoter hypermethylation is a common feature among many types of malignancies; it has been proposed that DNA methylation provides an alternative pathway to gene mutation.
Aims: To evaluate the promoter methylation in LMS: two tumour-related genes (MGMT and RASSF1A) were studied.
Materials and methods: 14 LMS specimens were obtained from patients treated at Orthopaedic Oncology and Reconstructive Surgery Department, CTO-CFR-M.Adelaide Hospital, Turin. Genomic DNA was extracted from paraffin sections and frozen samples according to standard protocols. Transformation of the methylations patterns in the CpG island of RASSF1A and MGMT of DNA were determined by chemical modification. To analyzed the role of aberrant DNA in LMS, methylation status by SP-PCR was evaluated. PCR products were amplified by unmethylated (U) and methylated (M)-specific primers.
Results: The RASSF1A promoter was methylated in 4 (29%) LMS, MGMT promoter was methylated in 2 (15 %); 1 of these patients with methylation had both RASSF1A and MGMT. Eight LMS samples did not show any methylation.
Conclusions: Our data indicate that inactivation of RASSF1A is a common event in LMS. Aberrant methylation of the RASSF1A promoter region is one of the most frequent epigenetic inactivation events detected in human cancer and leads to silencing of RASSF1A; moreover inactivation of RASSF1A was usually associated to poor prognosis. According to recent reports, that demonstrated that promoter hypermethylation of the MGMT gene is not a frequent event in LMS, the present study detected MGMT in 2 (15%) tumour samples.
The abstracts were prepared by incoming Professor Elena Brach del Prever. Correspondence should be addressed to IORS – President office, Dipartimento di Traumatologia, Ortopedia e Mediciana del Lavoro, Centro Traumatologico Ortopedico - Via Zuretti, 29 I-10135 Torino, Italy.
