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Abnormal Retention of Intron 9 in CD44 Gene Transcripts in Human Gastrointestinal Tumors¹

Nuffield Department of Pathology [K. Y., J. B., T. S., S. G., D. T.] and Department of Cellular Pathology [B. F. W], University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom; Department of Medical Oncology, National Cancer Center Hospital, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104, Japan [Y. M.]; and Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University [K. Y., T. T.], and First Department of Pathology, Hiroshima University School of Medicine [E. T.], 1-2-3 Kasumi, Minami-ku, Hiroshima 734, Japan

We have recently identified a new exon of the CD44 gene and demonstrated abnormal retention of a noncoding section, intron 9, in mRNA from bladder carcinomas. To analyze this further, the present study examined CD44 gene expression in cell lines from 14 esophageal, 3 colonic, and 4 breast carcinomas and in fresh samples from 20 colorectal carcinomas and corresponding normal colonic mucosa, using reverse transcriptase followed by the polymerase chain reaction (RT-PCR). This confirmed that there was abnormal assembly of several exons of the gene in cell lines and in tumor tissues from these organs. However, the most striking new finding was that intron 9 was present in RNA from 11 esophageal, 3 colon, and 1 breast carcinoma cell line, respectively. This was confirmed by RNase and DNase digestion analysis. Moreover, it was detected both in nuclear and cytoplasmic mRNA fractions, indicating that abnormal splicing of pre-mRNA occurs in cancer cells. The abnormal retention of intron 9 in CD44 gene transcripts was also demonstrated in tumor tissues from 16 (80%) of 20 patients with colon carcinoma, but there was no correlation with Dukes' stage. The biological significance of these observations is not yet understood. However, it is clear that, as with the abnormal expression pattern of CD44 variant exons, intron 9 retention is a good-candidate molecular diagnostic tool for colorectal carcinomas.

¹ This work was partly supported by a research contract between Boehringer Mannheim GmbH and Oxford University.

² To whom requests for reprints should be addressed.

Received 7/20/95. Accepted 8/17/95.

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