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Genetic analysis of cancer-implicated MicroRNA in ovarian cancer

Jennifer L Bearfoot1, David Y H Choong, Kylie L Gorringe

  • 1VBCRC Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Australia.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|November 18, 2008
PubMed
Abstract

Insights

Somatic mutations do not appear to be a common way microRNA genes are inactivated in ovarian cancer. Researchers found no mutations in 10 cancer-related microRNAs across 90 ovarian tumors.

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • MicroRNAs (miRNAs) are increasingly recognized for their role in cancer, potentially acting as tumor suppressors.
  • The specific mechanisms by which microRNA genes are inactivated in cancer cells remain largely unclear.

Purpose of the Study:

  • To investigate whether somatic mutations are a frequent mechanism for inactivating microRNA genes in ovarian cancer.
  • To analyze 10 specific microRNA genes implicated in cancer development.

Main Methods:

  • Analysis of 10 cancer-implicated microRNA genes for somatic mutations in 90 ovarian epithelial cancers and matched normal DNA.
  • Utilized high-resolution melt analysis and bidirectional sequencing to detect sequence variations.

Main Results:

  • No somatic mutations were identified in the analyzed microRNA genes within the cohort of ovarian tumors.
  • Numerous novel and known germline variations (substitutions, deletions, insertions) were found in regions flanking the mature microRNA sequences.
  • The frequency of these germline variants in non-cancer controls suggests they are not ovarian cancer-predisposing alleles.

Conclusions:

  • Somatic mutations appear to be an uncommon mechanism for microRNA gene inactivation in ovarian cancer.
  • Germline variations, rather than somatic mutations, are frequently observed in the vicinity of these microRNA genes.

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