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Frequent Abnormalities of the Putative Tumor Suppressor Gene FHIT at 3p14.2 in Pancreatic Carcinoma Cell Lines¹

Department of Internal Medicine, Division of Gastroenterology [B. S., N. P., K. M., A. B., R. A., B. G.], and Departments of Surgery [D. B.] and Pathology [P. B.], Philipps-University, 35033 Marburg, Germany

The FHIT gene is localized on chromosome 3p14, a region including a tumor cell-specific, commonly deleted region. To determine the role of the FHIT gene in pancreatic carcinogenesis, 14 pancreatic carcinoma cell lines were analyzed by reverse transcription-PCR and exon-specific PCR amplification of genomic DNA. The full-length FHIT transcript was lost in 70% of the pancreatic carcinoma cell lines analyzed, while 66% also revealed intragenic homozygous deletions of exons, 3, 4, and 5. Truncated FHIT transcripts lacking a variable number of exons most likely represented alternative splicing products. Fhit protein expression was dependent on a full-length FHIT transcript. The results suggest that the FHIT gene may be a target tumor suppressor gene involved in pancreatic carcinogenesis.

¹ This work was supported by grants from the Alfred und Ursula Kulemann Stiftung and the Deutsche Forschungsgemeinschaft, Grant Si 383/3-1 (to B. S.), and the Kempkes Stiftung and the Deutsche Forschungsgemeinschaft, Grant Ba 1487/2-1 (to D. B.).

² To whom requests for reprints should be addressed, at Department of Internal Medicine, Division of Gastroenterology and Endocrinology, Philipps University, Marburg/Germany. Phone: (49) 6421 28 2721; Fax: (49) 6421 28 2799; E-mail: simonb@post.med.uni-marburg.de.

Received 10/ 8/97. Accepted 2/18/98.

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