Frequent abnormalities of FHIT, a candidate tumor suppressor gene, in head and neck cancer cell lines.
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.
Department of Thoracic/Head & Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
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Mao
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Fan
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Lotan
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Hong
D017398:Alternative Splicing; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D017353:Gene Deletion; D015321:Gene Rearrangement; D016147:Genes, Tumor Suppressor / Q000235:genetics / Q000502:physiology*; D005819:Genetic Markers; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006867:Hydrolases; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic
D005819:Genetic Markers; D009363:Neoplasm Proteins; D011506:Proteins; C097552:histidine triad protein; D006867:Hydrolases