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Confined trisomy 8 mosaicism of meiotic origin: A rare cause of aneuploidy in childhood cancer.

Valind, Anders LU ; Pal, Niklas; Asmundsson, Jurate; Gisselsson Nord, David LU and Holmquist Mengelbier, Linda LU (2014) In Genes, Chromosomes and Cancer 53(7). p.634-638
Abstract
Whether chromosome abnormalities observed in tumor cells may in some cases reflect low-grade somatic mosaicism for anomalies present already at zygote formation, rather than acquired somatic mutations, has for long remained a speculation. We here report a patient with Wilms tumor, where constitutional somatic mosaicism of trisomy 8 was detected in a previously healthy 2 ½-year-old boy. Single Nucleotide Polymorphism (SNP) array analysis of tumor tissue revealed a complex distribution of allele frequencies for chromosome 8 that could not be explained solely by mitotic events. Combined analysis of allele frequencies, chromosome banding, and fluorescence in situ hybridization revealed that the majority of tumor cells contained four copies of... (More)
Whether chromosome abnormalities observed in tumor cells may in some cases reflect low-grade somatic mosaicism for anomalies present already at zygote formation, rather than acquired somatic mutations, has for long remained a speculation. We here report a patient with Wilms tumor, where constitutional somatic mosaicism of trisomy 8 was detected in a previously healthy 2 ½-year-old boy. Single Nucleotide Polymorphism (SNP) array analysis of tumor tissue revealed a complex distribution of allele frequencies for chromosome 8 that could not be explained solely by mitotic events. Combined analysis of allele frequencies, chromosome banding, and fluorescence in situ hybridization revealed that the majority of tumor cells contained four copies of chromosome 8, with three distinct haplotypes at a 2:1:1 ratio. Because the patient had not been subject to organ transplantation, these findings indicated that the tumor karyotype evolved from a cell with trisomy 8 of meiotic origin, with subsequent somatic gain of one additional chromosome copy. Haplotype analysis was consistent with trisomy 8 through nondisjunction at meiosis I. Matched normal renal tissue or peripheral blood did not contain detectable amounts of cells with trisomy 8, consistent with the complete lack of mosaic trisomy 8 syndrome features in the patient. This case provides proof of principle for the hypothesis that tumor genotypes may in rare cases reflect meiotic rather than mitotic events, also in patients lacking syndromic features. © 2014 Wiley Periodicals, Inc. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genes, Chromosomes and Cancer
volume
53
issue
7
pages
634 - 638
publisher
John Wiley & Sons
external identifiers
  • pmid:24729308
  • wos:000336500200010
  • scopus:84899919358
ISSN
1045-2257
DOI
10.1002/gcc.22173
language
English
LU publication?
yes
id
c7a5e6dc-c33f-457b-9d89-1f3abeaa4abc (old id 4430141)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24729308?dopt=Abstract
date added to LUP
2014-05-05 20:18:18
date last changed
2017-02-05 03:10:19
@article{c7a5e6dc-c33f-457b-9d89-1f3abeaa4abc,
  abstract     = {Whether chromosome abnormalities observed in tumor cells may in some cases reflect low-grade somatic mosaicism for anomalies present already at zygote formation, rather than acquired somatic mutations, has for long remained a speculation. We here report a patient with Wilms tumor, where constitutional somatic mosaicism of trisomy 8 was detected in a previously healthy 2 ½-year-old boy. Single Nucleotide Polymorphism (SNP) array analysis of tumor tissue revealed a complex distribution of allele frequencies for chromosome 8 that could not be explained solely by mitotic events. Combined analysis of allele frequencies, chromosome banding, and fluorescence in situ hybridization revealed that the majority of tumor cells contained four copies of chromosome 8, with three distinct haplotypes at a 2:1:1 ratio. Because the patient had not been subject to organ transplantation, these findings indicated that the tumor karyotype evolved from a cell with trisomy 8 of meiotic origin, with subsequent somatic gain of one additional chromosome copy. Haplotype analysis was consistent with trisomy 8 through nondisjunction at meiosis I. Matched normal renal tissue or peripheral blood did not contain detectable amounts of cells with trisomy 8, consistent with the complete lack of mosaic trisomy 8 syndrome features in the patient. This case provides proof of principle for the hypothesis that tumor genotypes may in rare cases reflect meiotic rather than mitotic events, also in patients lacking syndromic features. © 2014 Wiley Periodicals, Inc.},
  author       = {Valind, Anders and Pal, Niklas and Asmundsson, Jurate and Gisselsson Nord, David and Holmquist Mengelbier, Linda},
  issn         = {1045-2257},
  language     = {eng},
  number       = {7},
  pages        = {634--638},
  publisher    = {John Wiley & Sons},
  series       = {Genes, Chromosomes and Cancer},
  title        = {Confined trisomy 8 mosaicism of meiotic origin: A rare cause of aneuploidy in childhood cancer.},
  url          = {http://dx.doi.org/10.1002/gcc.22173},
  volume       = {53},
  year         = {2014},
}