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Related Experiment Videos

Alternate splicing produces a novel cyclin D1 transcript

D C Betticher1, N Thatcher, H J Altermatt

  • 1CRC Department of Cancer Genetics, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK.

Oncogene
|September 7, 1995
PubMed
Summary

Alternate splicing of cyclin D1 (CCND1) mRNA creates a variant protein. A common genetic variation influences this splicing, impacting non-small cell lung cancer patient outcomes.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • Cyclin D1 (CCND1) is a key regulator of the cell cycle.
  • Alternative splicing of CCND1 mRNA can produce protein variants with altered functions.
  • Understanding CCND1 splicing is crucial for cancer research.

Purpose of the Study:

  • To investigate alternative splicing of the cyclin D1 (CCND1) gene.
  • To determine the impact of a common genetic polymorphism on CCND1 splicing.
  • To explore the association between CCND1 splicing variants and non-small cell lung cancer (NSCLC) prognosis.

Main Methods:

  • Northern blotting and Polymerase Chain Reaction (PCR) analysis of cDNA from various cell lines and tissues.
  • mRNA analysis from mononuclear cells, lung tumors, and normal lung tissue.

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  • Genotyping of patients with resectable non-small cell lung cancer.

    • Main Results:

    • Demonstrated alternative splicing of CCND1 mRNA, generating a variant transcript lacking splicing at the exon 4 boundary and encoding an altered protein.
    • Both standard and variant CCND1 transcripts are expressed in mononuclear cells, lung tumors, and normal tissues.
    • A frequent A/G polymorphism in the exon 4 splice donor region modulates CCND1 splicing in heterozygotes.
    • Preliminary NSCLC patient data suggests a correlation between genotype and poorer event-free survival, with an increased risk of local relapse.

    Conclusions:

    • Alternative splicing of CCND1 is a common event, influenced by a genetic polymorphism.
    • This splicing variation is associated with clinical outcomes in non-small cell lung cancer patients.
    • Further research is warranted to elucidate the functional impact of CCND1 splicing variants in cancer.