Study of FHIT transcripts in normal and malignant breast tissue.

Cytogenetic and molecular studies have suggested that the 3p14.2 chromosome subband contains tumor suppressor genes involved in the pathogenesis of many types of human cancers. Recently, the FHIT (fragile histidine triad) gene was identified in this part of chromosome 3 as a candidate suppressor gene, and abnormal transcripts of this gene have been observed in various human tumors, including breast tumors. However, several investigators have challenged the involvement of FHIT in human cancers, especially because of discrepancies between data obtained with various PCR strategies and the observation that FHIT is alternatively spliced in normal tissues. We examined FHIT gene transcripts in a panel of normal (n = 27) and malignant (n = 33) breast tissue samples using single-stage PCR and two nested PCR strategies. In addition to a normal transcript, multiple variant transcripts were found at very low levels (<1% of the wild-type FHIT transcript) in the majority of the breast tumors, but also in adjacent normal breast tissues and normal breast tissue from women without cancer. These results do not support the involvement of the FHIT gene in breast tumorigenesis.