title: Recurrent inactivating mutations of ARID2 in non-small cell lung carcinoma.
abstract: In eukaryotic cells, DNA is packaged into chromatin and this compact storage in the nucleus promotes transcriptional repression of genes. Chromatin remodeling complexes such as the SWI/SNF complex are involved in making DNA accessible to transcription factors and thereby are implicated in the regulation of gene expression. Mutations and altered expression of chromatin remodeling complex genes have been described in cancer cells. Indeed, non-small cell lung cancer cell lines have been shown to harbor mutations in SMARCA4 (BRG1), a member of the SWI/SNF complex, but evidence has been less clear in primary tumors. Recently, inactivating mutations in AT-rich interaction domain 2 (ARID2) were found in liver cancer related to HCV infection and in melanoma. Here, we explored, using a genome-wide strategy and subsequent sequencing of targeted genes, whether chromatin remodeling is implicated in primary lung adenocarcinoma. Two genes were individualized from the genome screening as homozygously deleted in a set of samples: JARID2 and ARID2. Subsequent analysis of the entire coding sequences showed that ARID2 loss-of-function mutations were found in 5% of nonsmall cell lung cancers, thereby constituting one of the most frequently mutated genes in this cancer type after TP53, KRAS, EGFR, CDKN2A and STK11.
authors.affiliation: Molecular Basis of Response to Xenobiotics, INSERM UMR-S775, Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Manceau
authors.forename: Eric
authors.initials: E
authors.lastname: Letouzé
authors.forename: Cécile
authors.initials: C
authors.lastname: Guichard
authors.forename: Audrey
authors.initials: A
authors.lastname: Didelot
authors.forename: Aurelie
authors.initials: A
authors.lastname: Cazes
authors.forename: Hélène
authors.initials: H
authors.lastname: Corté
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fabre
authors.forename: Karine
authors.initials: K
authors.lastname: Pallier
authors.forename: Sandrine
authors.initials: S
authors.lastname: Imbeaud
authors.forename: Françoise
authors.initials: F
authors.lastname: Le Pimpec-Barthes
authors.forename: Jessica
authors.initials: J
authors.lastname: Zucman-Rossi
authors.forename: Pierre
authors.initials: P
authors.lastname: Laurent-Puig
authors.forename: Hélène
authors.initials: H
authors.lastname: Blons
mesh_terms: D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D018287:Carcinoma, Large Cell / Q000235:genetics* / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D042002:Chromatin Assembly and Disassembly; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D063151:Polycomb Repressive Complex 2 / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C512511:ARID2 protein, human; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C547777:JARID2 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; D063151:Polycomb Repressive Complex 2