High frequency of the HRAS oncogene codon 12 mutation in Macedonian patients with urinary bladder cancer

Abstract

Point mutations at codon 12 of the HRAS (v-Ha-ras Harvey rat sarcoma viral oncogene homolog) oncogene are one of the best defined and widely studied molecular genetic events in transitional cell carcinoma (TCC) of the urinary bladder. The aim of this study was to use the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of paraffin-embedded tissue-derived DNA to determine the frequency of the HRAS oncogene G →T codon 12 mutation in TCC patients being treated at the University Urology Clinic in Skopje, Republic of Macedonia. DNA isolated from paraffin-embedded tissue (PET) surgically removed TCC specimens of 62 (81.58%) out of 76 patients were successfully amplified, the remaining 14 (18.42%) showing compromised DNA integrity. The codon 12 mutation of the HRAS oncogene was found in 24 (38.71%) out of 62 successfully tested TCC urinary bladder samples. No significant relationship between the mutation frequency and the histopathological grade of tumor differentiation was detected (χ 2 = 0.044; p = 0.978). The relatively high frequency of mutations found in our study was comparable with some of the previously reported data obtained by this and/or other PCR-based methods. This highly sensitive and specific PCR-RFLP analysis was demonstrated to be a suitable method for the detection of mutations at codon 12 of the HRAS oncogene in PET samples of urinary bladder TCC.

Aspectos biológicos e atividade tumorigênica da família proto-oncogênica Ras

“…Essas mutações acontecem freqüentemente nos códons 12, 13, 59 e 61 (DUURSMA; AGAMI, 2003), mas são mais comuns no códon 12 -cerca de 90% (COTTI et al, 2000). Em N-RAS, são mais freqüentes no códon 61 (REUTER; MORGAN; BERGMANN, 2000) e em H-RAS, no códon 12 (CONEJO et al, 1998;PANOV et al, 2004). …”