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Accumulation of Immature Intron-containing CD44 Gene Transcripts in Breast Cancer Tissues.
1Nuffield Department of Pathology and Bacteriology, University of Oxford, Headington, Oxford, U.K.
Molecular Diagnosis : a Journal Devoted to the Understanding of Human Disease Through the Clinical Application of Molecular Biology
|September 1, 1996
Summary
Disorderly CD44 gene expression in breast cancer involves abnormal splicing and intron retention, indicating widespread gene regulation issues. This molecular abnormality may aid in diagnosing premalignant lesions and improving patient prognosis.
Area of Science:
- Molecular Biology
- Oncology
- Gene Expression Regulation
Background:
- Disordered CD44 gene expression is common in human malignancies.
- The reasons for diverse, abundant, and large CD44 transcripts are being investigated.
Purpose of the Study:
- To investigate CD44 gene expression in breast cancer tissues.
- To identify alternative splicing and intron retention in CD44 transcripts.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot hybridization.
- Analysis of fresh tissue samples from 21 breast cancers and 11 non-neoplastic controls.
- Use of probes targeting CD44 exons and intron 9.
Main Results:
- Breast cancer tissues showed elevated CD44 transcripts with unusual spliced variants and intron retention.
- Intron 9 retention was detected in 67% of tumor samples versus 27% of normal tissues.
- All tested exons were involved in the overexpression of CD44 in cancer tissues.
Conclusions:
- Breast cancer exhibits profound dysregulation in CD44 pre-messenger RNA (mRNA) production, splicing, and processing.
- These molecular abnormalities in CD44 are characteristic of neoplasia.
- Analyzing these abnormalities in suspected lesions may improve prognosis and treatment optimization.