Fragile histidine triad transcription abnormalities and human papillomavirus16 infection in human cervical carcinoma

Objective: To evaluate the relationship between fragile histidine triad (FHIT) transcription abnormalities and HPV16 infection and human cervical tumorigenesis. Methods: Total RNA from 5 cervical carcinoma cell lines (SiHa, HeLa, RJC-1, CS1213 and C4-1), 58 primary cervical cancer specimens and 18 normal cervical epithelial tissues were extracted and FHIT transcripts were characterized by a two-step (nested) reverse transcription (RT)-PCR. The seven of the PCR products with different size were purified and sequenced. HPV16 infection was assessed by PCR. Results: Circled digit one There were altered FHIT transcripts in SiHa, HeLa and C4-1 cells. Aberrant FHIT transcripts were detected in 39 out of the 58 cervical cancer samples (67.2%), but none out of 18 in the normal cervix tissue specimens (0%); HPV16 infections were identified in 37 of the 58 cervical cancer tissues (63.8%), but 1 in the 18 normal cervical epithelial tissues (5%), which showed a significant difference between these two groups (P < 0.05). Circled digit two The number of partial deletions of the FHIT gene in the group with HPV16 infection (29/37) was significantly higher than that in the group without HPV16 infection (9/21) and the correlation was found between aberration of FHIT transcript and HPV16 infection. There was no obvious difference in age, stage, tumor size, grade and lymph node metastasis between the groups with and without FHIT abnormalities and HPV16 infection (P>0.05). Circled digit three The exon 5 and exon 6 were mainly deleted in the altered FHIT transcripts and no insertion and point mutation were found by DNA sequencing. Conclusion: Aberrant FHIT expression was significantly common in cervical cancers and was correlated with HPV16 infection. These findings suggest that the tumor suppressor gene FHIT and high risk HPV16 may play a very important role in human cervical carcinogenesis.