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. Clin Cancer Res 2009 Mar 15;15(6):1923-30
Date
03/12/2009Pubmed ID
19276269Pubmed Central ID
PMC2668138DOI
10.1158/1078-0432.CCR-08-2091Scopus ID
2-s2.0-63549132021 (requires institutional sign-in at Scopus site) 176 CitationsAbstract
PURPOSE: 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.
EXPERIMENTAL DESIGN: 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.
Author List
Jackson EM, Sievert AJ, Gai X, Hakonarson H, Judkins AR, Tooke L, Perin JC, Xie H, Shaikh TH, Biegel JAAuthor
Xiaowu Gai PhD Chief, Director, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Chromosomal Proteins, Non-HistoneChromosomes, Human, Pair 22
DNA-Binding Proteins
Genes, Tumor Suppressor
Humans
In Situ Hybridization, Fluorescence
Loss of Heterozygosity
Nucleic Acid Amplification Techniques
Oligonucleotide Array Sequence Analysis
Polymorphism, Single Nucleotide
Rhabdoid Tumor
SMARCB1 Protein
Transcription Factors
