THE FHIT GENE AT 3P14.2 IS ABNORMAL IN BREAST CARCINOMAS

Chromosome 3p deletions in breast cancer have been detected at 3p12p21 by cytogenetic and loss of heterozygosity studies. Recently, we have cloned the FHIT (fragile histidine triad) gene, located at 3p14.2. Abn ormalities of the FHIT locus were found in many established cancer cel l lines, and the gene was abnormally transcribed in primary tumors of the digestive tract and lung. In this report, we describe the analysis of breast cancer, cell lines, and primary tumors for alterations in t ranscription of the FHIT gene; about 20% of the samples exhibited alte red transcripts. In most of the cases, aberrant transcripts were missi ng exons. Lack of expression of FHIT mRNA was observed in another 10% of primary tumor samples. These results suggest that alterations in th e FHIT gene may play an important role in breast cancer tumorigenesis and suggest that the FHIT gene product functions in the control of the tumorigenic phenotype in a large variety of human neoplasms.