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Title: Mitotic recombination of chromosome arm 17q as a cause of loss of heterozygosity of NF1 in neurofibromatosis type 1-associated glomus tumors
Authors: Stewart, Douglas R
Pemov, Alexander
Van Loo, Peter
Beert, Eline
Brems, Hilde
Sciot, Raf
Claes, Kathleen
Pak, Evgenia
Dutra, Amalia
Richard Lee, Chyi-Chia
Legius, Eric # ×
Issue Date: May-2012
Publisher: Wiley-Liss, Inc.
Series Title: Genes, Chromosomes & Cancer vol:51 issue:5 pages:429-437
Article number: 10.1002/gcc.21928
Abstract: Neurofibromatosis type 1 (NF1) is a common, autosomal dominant, tumor-predisposition syndrome that arises secondary to mutations in NF1. Glomus tumors are painful benign tumors that originate from the glomus body in the fingers and toes due to biallelic inactivation of NF1. We karyotyped cultures from four previously reported and one new glomus tumor and hybridized tumor (and matching germline) DNA on Illumina HumanOmni1-Quad SNP arrays (∼1 × 10(6) SNPs). Two tumors displayed evidence of copy-neutral loss of heterozygosity of chromosome arm 17q not observed in the germline sample, consistent with a mitotic recombination event. One of these two tumors, NF1-G12, featured extreme polyploidy (near-tetraploidy, near-hexaploidy, or near-septaploidy) across all chromosomes. In the remaining four tumors, there were few cytogenetic abnormalities observed, and copy-number analysis was consistent with diploidy in all chromosomes. This is the first study of glomus tumors cytogenetics, to our knowledge, and the first to report biallelic inactivation of NF1 secondary to mitotic recombination of chromosome arm 17q in multiple NF1-associated glomus tumors. We have observed mitotic recombination in 22% of molecularly characterized NF1-associated glomus tumors, suggesting that it is a not uncommon mechanism in the reduction to homozygosity of the NF1 germline mutation in these tumors. In tumor NF1-G12, we hypothesize that mitotic recombination also "unmasked" (reduced to homozygosity) a hypomorphic germline allele in a gene on chromosome arm 17q associated with chromosomal instability, resulting in the extreme polyploidy. © 2012 Wiley Periodicals, Inc.
URI: 
ISSN: 1045-2257
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Human Genome Laboratory
Laboratory for Neurofibromatosis Research
Translational Cell & Tissue Research
× corresponding author
# (joint) last author

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