A genome-wide screen for microdeletions reveals disruption of polarity complex genes in diverse human cancers.
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.
Rothenberg
S Michael
SM
Massachusetts General Hospital Cancer Center and Center for Molecular Therapeutics, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Mohapatra
Gayatry
G
Rivera
Miguel N
MN
Winokur
Daniel
D
Greninger
Patricia
P
Nitta
Mai
M
Sadow
Peter M
PM
Sooriyakumar
Gaya
G
Brannigan
Brian W
BW
Ulman
Matthew J
MJ
Perera
Rushika M
RM
Wang
Rui
R
Tam
Angela
A
Ma
Xiao-Jun
XJ
Erlander
Mark
M
Sgroi
Dennis C
DC
Rocco
James W
JW
Lingen
Mark W
MW
Cohen
Ezra E W
EE
Louis
David N
DN
Settleman
Jeffrey
J
Haber
Daniel A
DA
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
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; C509689:PARD3 protein, human; D012333:RNA, Messenger