RESPONSE TO RADIOTHERAPY OF HUMAN UTERINE CERVIX CARCINOMA IS NOT CORRELATED WITH REARRANGEMENTS OF THE HA-RAS-1 AND OR C-MYC GENES/

An association between the presence of the activated form of Ha-ras-1 and c-myc genes and increased cellular radioresistance had been shown in several cell lines. The aim of this study was to determine whether such an association could be observed in clinical tumour biopsies. We examined 70 tumour specimens and 51 samples of peripheral blood obtain ed from untreated patients with carcinoma of the uterine cervix mainly stage II and III. In addition to initial clinical tumour response to radiotherapy, radiosensitivity was also analysed by the subrenal capsu le assay (SRCA). Mutations in exons 1 and 2 of the Ha-ras-1 gene were examined using PCR single-strand conformation polymorphism (PCR-SSCP) and direct sequencing; adn restriction fragment length polymorphism of the Ha-ras-1 gene was analysed using Southern hybridisation. Eight (1 1%) out of 70 tumours contained mutations in exons 1 and 2 of the Ha-r as-1 gene. Eleven (22%) out of the 51 tumours displayed rearrangements of the Ha-ras-1 gene (six tumours (12%) showed alterations of allele length, one amplification and four (8%) loss of one Ha-ras-1 allele). In addition 12 (17%) out of 70 patients demonstrated the presence of r are alleles. Only one of the 70 tumours contained an amplified c-myc g ene. There was no significant correlation between either rearrangement s of the structure of the Ha-ras-1 and/or c-myc genes of presence of r are alleles in tumours and tumour response to radiotherapy. (C) 1997 E lsevier Science Ltd.