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FHIT Mutations in Human Primary Gastric Cancer

Laboratory of Human Carcinogenesis, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255 [A. G., K. H., L. M. B., M. A. K., M. N., W. P. B., C. C. H.]; and School of Oncology, Beijing Medical University, Beijing 100034, China [Y. K.]

Allelic deletion of multiple regions on the short arm of chromsome 3 (3p) implies the presence of multiple important tumor suppressor genes in human carcinogenesis. The FHIT gene, identified recently in chromosome 3p14.2, shows frequent allelic deletion and aberrant transcripts in gastrointestinal tumors. After determining the intron sequences flanking each of the coding exons of the FHIT gene and designing intron primers to facilitate mutation analysis of genomic DNA samples, we analyzed the complete coding sequences in matched cancer and normal tissues from 40 cases with primary gastric cancer using intron primers, PCR-signlestrand conformation polymorphism analysis, and direct sequencing. A somatic missense mutation in exon 6, codon 61, ACG (threonine) ATG (methionine) was found in a signet ring cell adenocarcinoma. We also evaluated allelic deletion in these tumors by PCR-based microsatellite analysis; allelic deletion occurred in 42.1% (16 of 38) of evaluable cases. This is the first report of a somatic missense mutation of the FHIT gene in a primary tumor. Presence of a point mutation and frequent allelic deletions are consistent with the hypothesis that FHIT gene alterations are involved in the development of primary gastric cancers.

¹ To whom requests for reprints should be addressed, at Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Building 37, Room 2C05, 37 Convent Drive, MSC 4255, Bethesda, MD 20892-4255. Phone: (301) 406-2048; Fax: (301) 496-0497; E-mail: Curtis_Harris@nih.gov.

Received 10/22/96. Accepted 2/28/97.

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