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High resolution SNP array profiling identifies variability in retinoblastoma genome stability
Author(s) -
Mol Berber M.,
Massink Maarten P. G.,
van der Hout Annemarie H.,
Dommering Charlotte J.,
Zaman Johannes M. A.,
Bosscha Machteld I.,
Kors Wijnanda A.,
MeijersHeijboer Hanne E.,
Kaspers Gertjan J. L.,
Riele Hein te,
Moll Annette C.,
Cloos Jacqueline,
Dorsman Josephine C.
Publication year - 2014
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22111
Subject(s) - loss of heterozygosity , retinoblastoma , biology , genetics , chromosome , chromosome 13 , snp array , single nucleotide polymorphism , copy number variation , microbiology and biotechnology , cancer research , gene , genome , allele , genotype
Both hereditary and nonhereditary retinoblastoma (Rb) are commonly initiated by loss of both copies of the retinoblastoma tumor suppressor gene ( RB1 ), while additional genomic changes are required for tumor initiation and progression. Our aim was to determine whether there is genomic heterogeneity between different clinical Rb subtypes. Therefore, 21 Rb tumors from 11 hereditary patients and 10 nonhereditary Rb patients were analyzed using high‐resolution single nucleotide polymorphism (SNP) arrays and gene losses and gains were validated with Multiplex Ligation‐dependent Probe Amplification. In these tumors only a few focal aberrations were detected. The most frequent was a focal gain on chromosome 2p24.3, the minimal region of gain encompassing the oncogene MYCN . The genes BAZ1A , OTX2 , FUT8 , and AKT1 were detected in four focal regions on chromosome 14 in one nonhereditary Rb. There was a large difference in number of copy number aberrations between tumors. A subset of nonhereditary Rbs turned out to be the most genomic unstable, while especially very young patients with hereditary Rb display stable genomes. Established Rb copy number aberrations, including gain of chromosome arm 1q and loss of chromosome arm 16q, turned out to be preferentially associated with the nonhereditary Rbs with later age of diagnosis. In contrast, copy number neutral loss of heterozygosity was detected mainly on chromosome 13, where RB1 resides, irrespective of hereditary status or age. Focal amplifications and deletions and copy number neutral loss of heterozygosity besides chromosome 13 appear to be rare events in retinoblastoma. © 2013 Wiley Periodicals, Inc.