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High grade sarcomas are associated with microsatellite instability (chromosom 12) and loss of heterozygosity (chromosom 2)

Monika Rucińska, Leszek Kozłowski, Witold Pepiński, Małgorzata Skawrońska, Jerzy Janica, Marek Z. Wojtukiewicz

Med Sci Monit 2005; 11(2): BR65-68

ID: 14145

Background:The genetic changes in DNA microsatellites – short, tandem repeat segments dispersed throughout the human genome – probably play a role in carcinogenesis. Microsatellite instability (MSI) is reflected in alterations in the patterns of these polymorphic repeat segments. In our study, human sarcomas were analyzed for the presence of microsatellite instability and loss of heterozygosity (LOH).Material/Methods:Studies were performed on tissue specimens obtained at surgical resection from 20 patients with malignant and non-malignant soft tissue tumors (8 G1 sarcomas, 8 G3 sarcomas, 2 lipomas and 2 fibromas). Samples of venous blood from the patients served as respective controls. DNA was isolated using organic extraction. Additional microcolumn purification was performed. Fluorescent multiplex polymerase chain reaction (PCR) was used to amplify 10 microsatellite loci included in commercially available human identification kits. Microsatellite marker BAT 26 was amplified in separate PCR reactions.Results:All the G3 sarcomas manifested MSI. MSI was detected on 12p in all the specimens except for recurrent synovial sarcomas. LOH in BAT 26 analysis (chromosome 2) was present in 75% of G3 sarcomas. No MSI or LOH was found in G1 sarcomas or in benign tumors.Conclusions:Genomic instability may contribute to tumorgenesis in sarcomas, and both MSI and LOH may reflect genomic instability in sarcomas. These parameters may be helpful in the differential diagnosis of malignant versus nonmalignant lesions.

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