THE FHIT GENE AT 3P14.2 IS ABNORMAL IN LUNG-CANCER

To determine the role of the FHIT gene, which encompasses the fragile site at 3p14.2, we analyzed 59 tumors of the small cell and non-small cell type by reverse transcription of FHIT mRNA, followed by PCR ampli fication and sequencing of products. Allelic losses affecting the gene were evaluated by microsatellite polymorphism analysis and genomic al terations by hybridization using cDNA and genomic probes. Small cell l ung tumors (80%) and non-small cell lung cancers (40%) showed abnormal ities in RNA transcripts of FHIT, and 76% of the tumors exhibited loss of FHIT alleles. Abnormal lung tumor transcripts lack two or more exo ns of the FHIT gene. Small cell lung cancer tumors and cell lines were analyzed by Southern blotting and showed rearranged BamHI fragments. These data suggest a critical role of the FHIT gene in lung carcinogen esis.