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Genetic heterogeneity in rhabdomyosarcoma revealed by SNP array analysis.

Walther, Charles LU ; Mayrhofer, Markus; Nilsson, Jenny LU ; Hofvander, Jakob LU ; Jonson, Tord LU ; Mandahl, Nils LU ; Øra, Ingrid LU ; Gisselsson Nord, David LU and Mertens, Fredrik LU (2016) In Genes, Chromosomes and Cancer 55(1). p.3-15
Abstract
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents. Alveolar (ARMS) and embryonal (ERMS) histologies predominate, but rare cases are classified as spindle cell/sclerosing (SRMS). For treatment stratification, RMS is further subclassified as fusion-positive (FP-RMS) or fusion-negative (FN-RMS), depending on whether a gene fusion involving PAX3 or PAX7 is present or not. We investigated 19 cases of pediatric RMS using high resolution single-nucleotide polymorphism (SNP) array. FP-ARMS displayed, on average, more structural rearrangements than ERMS; the single FN-ARMS had a genomic profile similar to ERMS. Apart from previously known amplification (e.g., MYCN, CDK4, and MIR17HG) and deletion (e.g., NF1,... (More)
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents. Alveolar (ARMS) and embryonal (ERMS) histologies predominate, but rare cases are classified as spindle cell/sclerosing (SRMS). For treatment stratification, RMS is further subclassified as fusion-positive (FP-RMS) or fusion-negative (FN-RMS), depending on whether a gene fusion involving PAX3 or PAX7 is present or not. We investigated 19 cases of pediatric RMS using high resolution single-nucleotide polymorphism (SNP) array. FP-ARMS displayed, on average, more structural rearrangements than ERMS; the single FN-ARMS had a genomic profile similar to ERMS. Apart from previously known amplification (e.g., MYCN, CDK4, and MIR17HG) and deletion (e.g., NF1, CDKN2A, and CDKN2B) targets, amplification of ERBB2 and homozygous loss of ASCC3 or ODZ3 were seen. Combining SNP array with cytogenetic data revealed that most cases were polyploid, with at least one case having started as a near-haploid tumor. Further bioinformatic analysis of the SNP array data disclosed genetic heterogeneity, in the form of subclonal chromosomal imbalances, in five tumors. The outcome was worse for patients with FP-ARMS than ERMS or FN-ARMS (6/8 vs. 1/9 dead of disease), and the only children with ERMS showing intratumor diversity or with MYOD1 mutation-positive SRMS also died of disease. High resolution SNP array can be useful in evaluating genomic imbalances in pediatric RMS. © 2015 Wiley Periodicals, Inc. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genes, Chromosomes and Cancer
volume
55
issue
1
pages
3 - 15
publisher
John Wiley & Sons
external identifiers
  • pmid:26482321
  • wos:000368259400001
  • scopus:84954397976
ISSN
1045-2257
DOI
10.1002/gcc.22285
language
English
LU publication?
yes
id
9519015e-fb85-4ee6-854d-d1d7dbb84a31 (old id 8148872)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26482321?dopt=Abstract
date added to LUP
2015-11-03 18:29:26
date last changed
2017-07-09 03:12:44
@article{9519015e-fb85-4ee6-854d-d1d7dbb84a31,
  abstract     = {Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents. Alveolar (ARMS) and embryonal (ERMS) histologies predominate, but rare cases are classified as spindle cell/sclerosing (SRMS). For treatment stratification, RMS is further subclassified as fusion-positive (FP-RMS) or fusion-negative (FN-RMS), depending on whether a gene fusion involving PAX3 or PAX7 is present or not. We investigated 19 cases of pediatric RMS using high resolution single-nucleotide polymorphism (SNP) array. FP-ARMS displayed, on average, more structural rearrangements than ERMS; the single FN-ARMS had a genomic profile similar to ERMS. Apart from previously known amplification (e.g., MYCN, CDK4, and MIR17HG) and deletion (e.g., NF1, CDKN2A, and CDKN2B) targets, amplification of ERBB2 and homozygous loss of ASCC3 or ODZ3 were seen. Combining SNP array with cytogenetic data revealed that most cases were polyploid, with at least one case having started as a near-haploid tumor. Further bioinformatic analysis of the SNP array data disclosed genetic heterogeneity, in the form of subclonal chromosomal imbalances, in five tumors. The outcome was worse for patients with FP-ARMS than ERMS or FN-ARMS (6/8 vs. 1/9 dead of disease), and the only children with ERMS showing intratumor diversity or with MYOD1 mutation-positive SRMS also died of disease. High resolution SNP array can be useful in evaluating genomic imbalances in pediatric RMS. © 2015 Wiley Periodicals, Inc.},
  author       = {Walther, Charles and Mayrhofer, Markus and Nilsson, Jenny and Hofvander, Jakob and Jonson, Tord and Mandahl, Nils and Øra, Ingrid and Gisselsson Nord, David and Mertens, Fredrik},
  issn         = {1045-2257},
  language     = {eng},
  number       = {1},
  pages        = {3--15},
  publisher    = {John Wiley & Sons},
  series       = {Genes, Chromosomes and Cancer},
  title        = {Genetic heterogeneity in rhabdomyosarcoma revealed by SNP array analysis.},
  url          = {http://dx.doi.org/10.1002/gcc.22285},
  volume       = {55},
  year         = {2016},
}