STUDY OF FHIT TRANSCRIPTS IN NORMAL AND MALIGNANT BREAST-TISSUE

Cytogenetic and molecular studies have suggested that the 3p14.2 chrom osome subband contains tumor suppressor genes involved in the pathogen esis of many types of human cancers. Recently, the FHIT (fragile histi dine triad) gene was identified in this part of chromosome 3 as a cand idate suppressor gene, and abnormal transcripts of this gene have been observed in various human tumors, including breast tumors. However, s everal investigators have challenged the involvement of FHIT in human cancers, especially because of discrepancies between data obtained wit h various PCR stategies and the observation that FHIT is alternatively spliced in normal tissues. We examined FHIT gene transcripts in a pan el of normal (n = 27) and malignant (n = 33) breast tissue samples usi ng single-stage PCR and two nested PCR strategies. In addition to a no rmal transcript, multiple variant transcripts were found at very low l evels (<1% of the wild-type FHIT transcript) in the majority of the br east tumors, but also in adjacent normal breast tissues and normal bre ast tissue from women without cancer. These results do not. support th e involvement of the FHIT gene in breast tumorigenesis. Genes Chromoso mes Cancer 23:292-299, 1998. (C) 1998 Wiley-Liss, Inc.