High-resolution genomic analysis suggests the absence of recurrent genomic alterations other than SMARCB1 aberrations in atypical teratoid/rhabdoid tumors.
Atypical teratoid/rhabdoid tumor (AT/RT) is a rare malignant pediatric brain tumor characterized by genetic alterations affecting the SMARCB1 (hSNF5/INI1) locus in chromosome band 22q11.2. To identify potential additional genetic alterations, high-resolution genome-wide analysis was performed using a molecular inversion probe single-nucleotide polymorphism (MIP SNP) assay (Affymetrix OncoScan formalin-fixed paraffin-embedded express) on DNA isolated from 18 formalin-fixed paraffin-embedded archival samples. Alterations affecting the SMARCB1 locus could be demonstrated by MIP SNP in 15 out of 16 evaluable cases (94%). These comprised five tumors with homozygous deletions, six tumors with heterozygous deletions, and four tumors with copy number neutral loss of heterozygosity (LOH) involving chromosome band 22q11.2. Remarkably, MIB SNP analysis did not yield any further recurrent chromosomal gains, losses, or copy neutral LOH. On MIP SNP screening for somatic mutations, the presence of a SMARCB1 mutation (c.472C>T p.R158X) was confirmed, but no recurrent mutations of other cancer relevant genes could be identified. Results of fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, and SMARCB1 sequencing were highly congruent with that of the MIP SNP assay. In conclusion, these data further suggest the absence of recurrent genomic alterations other than SMARCB1 in AT/RT.
Institute of Neuropathology, University Hospital Münster, Münster, Germany. hasselblatt@uni-muenster.de
Martin
M
Hasselblatt
Sarah
S
Isken
Anna
A
Linge
Kristin
K
Eikmeier
Astrid
A
Jeibmann
Florian
F
Oyen
Inga
I
Nagel
Julia
J
Richter
Kerstin
K
Bartelheim
Uwe
U
Kordes
Reinhard
R
Schneppenheim
Michael
M
Frühwald
Reiner
R
Siebert
Werner
W
Paulus
D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D002869:Chromosome Aberrations; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D019656:Loss of Heterozygosity; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D018335:Rhabdoid Tumor / Q000235:genetics*; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000235:genetics*
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors