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

In a genome-wide screen of human cancer cell lines, we identified homozygous intragenic microdeletions involving genes encoding components of the apical-basal cell polarity complexes. Among these, PARD3 is disrupted in cell lines and primary tumors from squamous carcinomas and glioblastomas. Reconstituting PARD3 expression in both cell types restores tight junctions and retards contact-dependent proliferation. Searching specifically for small intragenic microdeletions using high-resolution genomic arrays may be complementary to other genomic deletion screens and resequencing efforts in identifying new tumor suppressor genes. 444 human cancer cell lines of diverse tissue origin and 6 EBV-transformed B-lymphocyte cell lines (Coriell Institute for Medical Research, Camden, NJ) as controls.