title: Genome-wide approach to identify second gene targets for malignant rhabdoid tumors using high-density oligonucleotide microarrays.
abstract: Malignant rhabdoid tumor (MRT) is a rare and highly lethal cancer that mainly affects infants and young children. The majority of MRT are characterized by loss of function of SMARCB1 on chromosome 22q11.2. However, little is known about genetic changes other than SMARCB1 alterations that are responsible for the development and/or progression of MRT. To explore additional gene targets in MRT, we analyzed 21 MRT specimens (12 fresh tumors and 9 MRT-derived cell lines) using high-density single nucleotide polymorphism genotyping microarrays. Although MRT genomes are characterized by common 22q11.2 deletions, affecting the SMARCB1 locus with a frequency of 95.2% (20/21 specimens), other genetic changes have been less frequent. Of the 20 specimens with deletions of 22q11.2, eight specimens showed uniparental disomy of the SMARCB1 locus with homozygous deletions or gene mutations. High-resolution analysis also disclosed the recurrent hemizygous/homozygous deletions of 7q35-q36.1, involving the CNTNAP2 locus in three specimens. Mutations analysis of CNTNAP2 showed a novel R157C missense mutation in a primary case, and methylation analysis showed recurrent hypermethylation of CNTNAP2 in three of nine cell lines. These results demonstrated that CNTNAP2 is one of the additional gene targets, other than SMARCB1, in MRT.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Takita
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Chen
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kato
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ohki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sato
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ohta
authors.forename: Kanji
authors.initials: K
authors.lastname: Sugita
authors.forename: Riki
authors.initials: R
authors.lastname: Nishimura
authors.forename: Noriko
authors.initials: N
authors.lastname: Hoshino
authors.forename: Masafumi
authors.initials: M
authors.lastname: Seki
authors.forename: Masashi
authors.initials: M
authors.lastname: Sanada
authors.forename: Akira
authors.initials: A
authors.lastname: Oka
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D056915:DNA Copy Number Variations; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D018335:Rhabdoid Tumor / Q000235:genetics*; D000071796:SMARCB1 Protein; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C403049:CNTNAP2 protein, human; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors
keywords: CNTNAP2; SMARCB1; SNP array; malignant rhabdoid tumor