ANALYSIS OF FHIT TRANSCRIPTS IN CERVICAL AND ENDOMETRIAL CANCERS

Carcinoma of the uterine cervix is a common malignancy, and many affec ted women, have been found to exhibit loss of heterozygosity (LOH) in the chromosome 3p region. Recent studies have localized the FHIT (frag ile histidine triad) gene in this region and also demonstrated a high frequency of abnormalities of this gene in various cancers. To determi ne the role of the FHIT gene in cervical and uterine carcinomas, 16 ca ses of cervical carcinoma and 7 cases of endometrial carcinoma, as wel l as nearby non-cancerous tissues in these patients, were analyzed by reverse transcription of the FHIT mRNA followed by polymerase chain re action amplification and sequencing of the products. In this study, 13 of 16 cervical cancers and 4 of 7 endometrial cancers displayed abnor mal 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. Moreo ver, 5 of 16 matched noncancerous tissues from the cervical cancer pat ients and 4 of 7 non-cancerous tissues from endometrial cancer patient s also showed the presence of abnormal transcripts lacking 3 or more e xons of the FHIT gene. Only 1 of 23 paired samples exhibited LOH. Our results suggest that the abnormal transcript of the FHIT gene is commo n in both normal and tumor tissues of the uterus and cervix. We also c hecked for HPV infection in these samples and found no definite relati onship between the abnormal transcript and human papillomavirus infect ion. (C) 1998 Wiley-Liss, Inc.