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Related Experiment Videos

Multiple intron retention occurs in tumor cell CD44 mRNA processing

S Goodison1, K Yoshida, M Churchman

  • 1UCSD Cancer Center, University of California, San Diego, La Jolla, USA.

The American Journal of Pathology
|October 20, 1998
PubMed
Summary

Aberrant CD44 messenger RNA (mRNA) processing, including intron retention, is common in colorectal tumors. This study shows intron 18 retention in 75% of carcinomas, indicating widespread CD44 gene expression abnormalities in cancer.

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Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Increased CD44 transcripts and proteins are observed in many tumors.
  • Aberrant CD44 variable exon expression is linked to tumor growth and metastasis.
  • Previous work noted intron 9 inclusion in CD44 mRNA from tumor tissues.

Purpose of the Study:

  • To investigate if intron retention in CD44 mRNA is a general phenomenon in tumor cells.
  • To assess the specificity of intron retention for particular introns within the CD44 gene.
  • To characterize CD44 intron 18 and its processing in colorectal tumors.

Main Methods:

  • Cloning and sequencing of CD44 intron 18 from genomic DNA.
  • Analysis of novel sequences and creation of intron 18-specific probes.

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  • Assessment of CD44 intron 18 retention/excision in a colon tumor cell line (HT29) and 20 colorectal tumor/normal tissue pairs using RT-PCR or similar techniques.
  • Main Results:

    • CD44 intron 18 was retained in transcripts from 75% of colorectal carcinomas (15/20).
    • Intron 18 retention was significantly less frequent in matched normal tissues (15%, 3/20).
    • These findings are consistent with high intron 9 retention (80%) previously observed in colonic carcinoma mRNA.

    Conclusions:

    • Multiple abnormalities in CD44 mRNA processing, including intron retention, occur in tumor cells.
    • Intron 18 retention is a frequent event in colorectal carcinomas.
    • Aberrant CD44 mRNA processing is a potentially widespread characteristic of cancer gene expression.