title: A genome-wide screen for microdeletions reveals disruption of polarity complex genes in diverse human cancers.
abstract: In a genome-wide screen of 684 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.
authors.affiliation: Massachusetts General Hospital Cancer Center and Center for Molecular Therapeutics, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
authors.forename: S Michael
authors.initials: SM
authors.lastname: Rothenberg
authors.forename: Gayatry
authors.initials: G
authors.lastname: Mohapatra
authors.forename: Miguel N
authors.initials: MN
authors.lastname: Rivera
authors.forename: Daniel
authors.initials: D
authors.lastname: Winokur
authors.forename: Patricia
authors.initials: P
authors.lastname: Greninger
authors.forename: Mai
authors.initials: M
authors.lastname: Nitta
authors.forename: Peter M
authors.initials: PM
authors.lastname: Sadow
authors.forename: Gaya
authors.initials: G
authors.lastname: Sooriyakumar
authors.forename: Brian W
authors.initials: BW
authors.lastname: Brannigan
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ulman
authors.forename: Rushika M
authors.initials: RM
authors.lastname: Perera
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Angela
authors.initials: A
authors.lastname: Tam
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Ma
authors.forename: Mark
authors.initials: M
authors.lastname: Erlander
authors.forename: Dennis C
authors.initials: DC
authors.lastname: Sgroi
authors.forename: James W
authors.initials: JW
authors.lastname: Rocco
authors.forename: Mark W
authors.initials: MW
authors.lastname: Lingen
authors.forename: Ezra E W
authors.initials: EE
authors.lastname: Cohen
authors.forename: David N
authors.initials: DN
authors.lastname: Louis
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Settleman
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Haber
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D017353:Gene Deletion; D015894:Genome, Human; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019108:Tight Junctions / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; C509689:PARD3 protein, human; D012333:RNA, Messenger