title: Genomic analysis using high-density single nucleotide polymorphism-based oligonucleotide arrays and multiplex ligation-dependent probe amplification provides a comprehensive analysis of INI1/SMARCB1 in malignant rhabdoid tumors.
abstract: OBJECTIVE
  A high-resolution genomic profiling and comprehensive targeted analysis of INI1/SMARCB1 of a large series of pediatric rhabdoid tumors was done. The aim was to identify regions of copy number change and loss of heterozygosity (LOH) that might pinpoint additional loci involved in the development or progression of rhabdoid tumors and define the spectrum of genomic alterations of INI1 in this malignancy.
  
  
  METHODS
  A multiplatform approach using Illumina single nucleotide polymorphism-based oligonucleotide arrays, multiplex ligation-dependent probe amplification, fluorescence in situ hybridization, and coding sequence analysis was used to characterize genome-wide copy number changes, LOH, and genomic alterations of INI1/SMARCB1 in a series of pediatric rhabdoid tumors.
  
  
  RESULTS
  The biallelic alterations of INI1 that led to inactivation were elucidated in 50 of 51 tumors. INI1 inactivation was shown by a variety of mechanisms, including deletions, mutations, and LOH. The results from the array studies highlighted the complexity of rearrangements of chromosome 22 compared with the low frequency of alterations involving the other chromosomes.
  
  
  CONCLUSIONS
  The results from the genome-wide single nucleotide polymorphism array analysis suggest that INI1 is the primary tumor suppressor gene involved in the development of rhabdoid tumors with no second locus identified. In addition, we did not identify hotspots for the breakpoints in sporadic tumors with deletions of chromosome 22q11.2. By employing a multimodality approach, the wide spectrum of alterations of INI1 can be identified in the majority of patients, which increases the clinical utility of molecular diagnostic testing.
authors.affiliation: Department of Neurosurgery and Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Jackson
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Sievert
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Gai
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Judkins
authors.forename: Laura
authors.initials: L
authors.lastname: Tooke
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Perin
authors.forename: Hongbo
authors.initials: H
authors.lastname: Xie
authors.forename: Tamim H
authors.initials: TH
authors.lastname: Shaikh
authors.forename: Jaclyn A
authors.initials: JA
authors.lastname: Biegel
mesh_terms: D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22; D004268:DNA-Binding Proteins / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D018335:Rhabdoid Tumor / Q000235:genetics*; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors