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Frequent Abnormalities of FHIT, a Candidate Tumor Suppressor Gene, in Head and Neck Cancer Cell Lines¹

Departments of Thoracic/Head & Neck Medical Oncology [L. M., Y-H. F., W. K. H.] and Tumor Biology [R. L.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Loss of heterozygosity at the short arm of chromosome 3 occurs frequently in head and neck squamous cell carcinoma (HNSCC). FHIT, a candidate tumor suppressor gene, was recently identified at 3p14.2, and abnormalities of the gene were found in several types of human cancers. To investigate a potential role of the FHIT gene in HNSCC, we examined 16 HNSCC cell lines from 11 patients for abnormalities of the gene by using microsatellite analysis, reverse transcription-PCR, sequencing, and Southern blot analysis. We found that 13 of 16 (81%) cell lines exhibit loss of heterozygosity at 3p14.2. Seven cell lines from six individuals exhibited abnormal transcription patterns, including lack of a FHIT transcript in three lines and shortened transcripts in four lines. A further examination of coding sequences of FHIT in all lines with FHIT transcripts revealed a deletion of exon 4 in one line, a deletion of exons 5 to 7 in one line, and a deletion of exons 5 to 7 plus multiple small insertions between exons 4 and 8 in two lines derived from a primary tumor and a metastasis in the same individual. These results indicate that FHIT may have been inactivated in six cell lines from five (45%) individuals. We also observed two common polymorphism sites at codons 88 and 98 of the gene. These data indicate that abnormal transcription of the FHIT gene is common in HNSCC cell lines; however, other tumor suppressor gene(s) may reside at the same chromosomal region.

¹ This study was supported in part by an M. D. Anderson Cancer Center PRS grant and National Cancer Institute Grant PO1 CA 52051. W. K. H. is a American Cancer Society Clinical Research Professor.

² To whom requests for reprints should be addressed, at Department of Thoracic/Head & Neck Medical Oncology, Box 80, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

Received 7/12/96. Accepted 10/ 1/96.

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