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A genome-wide screen for microdeletions reveals disruption of polarity complex genes in diverse human cancers

S Michael Rothenberg1, Gayatry Mohapatra, Miguel N Rivera

  • 1Massachusetts General Hospital Cancer Center and Center for Molecular Therapeutics, Harvard Medical School, Charlestown, Massachusetts 02129, USA.

Cancer Research
|March 11, 2010
PubMed

Insights

Researchers found small gene deletions in cancer cell lines, particularly affecting cell polarity. Restoring the PARD3 gene halted cancer cell growth, suggesting a new approach for finding tumor suppressor genes.

Area of Science:

  • Genomics
  • Cancer Biology
  • Cell Polarity

Background:

  • Cancer cell proliferation is often driven by genetic alterations.
  • Cell polarity complexes play crucial roles in maintaining normal cell function and tissue architecture.
  • Disruptions in cell polarity are increasingly recognized in various cancers.

Purpose of the Study:

  • To identify genetic alterations associated with cancer cell proliferation.
  • To investigate the role of apical-basal cell polarity genes in cancer.
  • To explore novel methods for tumor suppressor gene discovery.

Main Methods:

  • Genome-wide screening of 684 cancer cell lines.
  • High-resolution genomic array analysis to detect intragenic microdeletions.
  • Gene expression reconstitution experiments in cancer cell lines and primary tumors.

Main Results:

  • Identified homozygous intragenic microdeletions in genes encoding apical-basal cell polarity complexes.
  • Found PARD3 gene disruption in squamous carcinoma and glioblastoma cell lines and tumors.
  • Restoring PARD3 expression normalized tight junctions and reduced proliferation in cancer cells.

Conclusions:

  • Intragenic microdeletions targeting cell polarity genes are implicated in cancer.
  • PARD3 is a potential tumor suppressor gene in squamous carcinomas and glioblastomas.
  • Targeted screening for microdeletions complements existing methods for tumor suppressor gene discovery.

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