A Study of Alveolar Rhabdomyosarcoma Copy Number Alterations by Single Nucleotide Polymorphism AnalysisLynn, Miriam PhD; Shah, Naisha PhD; Conroy, Judith PhD; Ennis, Sean PhD; Morris, Thomas BSc; Betts, David BSc; O’Sullivan, Maureen MB, MDApplied Immunohistochemistry & Molecular Morphology: March 2014 - Volume 22 - Issue 3 - p 213–221 doi: 10.1097/PDM.0000000000000030 Research Articles Abstract Author Information Rhabdomyosarcoma, the most common pediatric soft tissue malignancy arises in 2 major histologic forms: embryonal and alveolar. Classically, the alveolar subtype is characterized by a chromosomal translocation t(2;13)(q35;q14) or t(1;13)(p36;q14) fusing the PAX3 or PAX7 gene, respectively, to the FOXO1 gene, although fusion-negative cases of alveolar rhabdomyosarcoma (ARMS) occur; these share considerably more with the genomic profiles and biological behavior of embryonal rhabdomyosarcoma than with fusion-positive ARMS. The current understanding of any additional genetic aberrations in fusion-positive ARMS is limited. In this study, we evaluated tumor-specific copy number alterations in a cohort of fusion-positive ARMSs using high-resolution technology. The results presented here include previously described changes as well as completely novel findings of copy number alterations in BCR and DICER. The study furthermore highlights associations between fusion type and genotype, as well as outcomes and genotype. Rearrangement of PAX7 is strongly associated with copy number alteration of Glypican 5 (GPC5) and moderately with amplification of IGF1R. There is a moderate association between death from/relapse of disease and, on the one hand, amplification of 12q13.3 (DDIT3; Gli1), and on the other hand, copy number alteration of Wnt6 or LRP1B. Gains of both LRP1B and Gli1 in turn are strongly associated with MycN amplification. National Children’s Research Centre, Crumlin, Dublin, Ireland Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website, www.molecularpathology.com. The authors declare no conflict of interest. Reprints: Maureen O’Sullivan, MB, MD, Department of Histology, Our Lady’s Children’s Hospital Crumlin, Dublin 12, Ireland (e-mail: firstname.lastname@example.org). Received April 5, 2013 Accepted August 1, 2013 © 2014 Lippincott Williams & Wilkins, Inc.