Analysis of FHIT transcripts in cervical and endometrial cancers.

Abstract

Carcinoma of the uterine cervix is a common malignancy, and many affected women, have been found to exhibit loss of heterozygosity (LOH) in the chromosome 3p region. Recent studies have localized the FHIT (fragile histidine triad) gene in this region and also demonstrated a high frequency of abnormalities of this gene in various cancers. To determine the role of the FHIT gene in cervical and uterine carcinomas, 16 cases of cervical carcinoma and 7 cases of endometrial carcinoma, as well as nearby non-cancerous tissues in these patients, were analyzed by reverse transcription of the FHIT mRNA followed by polymerase chain reaction amplification and sequencing of the products. In this study, 13 of 16 cervical cancers and 4 of 7 endometrial cancers displayed abnormal FHIT transcripts, including a lack of 2 or more exons of the FHIT gene, the insertion of several bases in the deletion junctions, and a 282 bp deletion from cDNA 171 to 452, resulting in a frameshift. Moreover, 5 of 16 matched non-cancerous tissues from the cervical cancer patients and 4 of 7 non-cancerous tissues from endometrial cancer patients also showed the presence of abnormal transcripts lacking 3 or more exons of the FHIT gene. Only 1 of 23 paired samples exhibited LOH. Our results suggest that the abnormal transcript of the FHIT gene is common in both normal and tumor tissues of the uterus and cervix. We also checked for HPV infection in these samples and found no definite relationship between the abnormal transcript and human papillomavirus infection.