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Sarcoma
Volume 2013 (2013), Article ID 520858, 8 pages
http://dx.doi.org/10.1155/2013/520858
Research Article

MDM2 Amplification and PI3KCA Mutation in a Case of Sclerosing Rhabdomyosarcoma

1Pediatric Cancer Biology Program, Department of Pediatrics, Papé Family Pediatric Research Institute, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Road, Mail Code L321, Portland, OR 97239-3098, USA
2Department of Pathology, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Road, Mail Code L41, Portland, OR 97239-3098, USA
3Division of Hematology-Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA
4Department of Radiation Oncology, Oregon Health & Science University, Portland, OR 97239, USA
5Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97239, USA

Received 9 March 2013; Accepted 24 April 2013

Academic Editor: Cyril Fisher

Copyright © 2013 Ken Kikuchi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A rare sclerosing variant of rhabdomyosarcoma characterized by prominent hyalinization and pseudovascular pattern has recently been described as a subtype biologically distinct from embryonal, alveolar, and pleomorphic forms. We present cytogenetic and molecular findings as well as experimental studies of an unusual case of sclerosing rhabdomyosarcoma. The primary lesion arose within the plantar subcutaneous tissue of the left foot of an otherwise healthy 23-year-old male who eventually developed pulmonary nodules despite systemic chemotherapy. Two genetic abnormalities identified in surgical and/or autopsy samples of the tumor were introduced into 10T1/2 murine fibroblasts to determine whether these genetic changes cooperatively facilitated transformation and growth. Cytogenetic analysis revealed a complex abnormal hyperdiploid clone, and MDM2 gene amplification was confirmed by fluorescence in situ hybridization. Cancer gene mutation screening using a combination of multiplexed PCR and mass spectroscopy revealed a PIK3CA exon 20 H1047R mutation in the primary tumor, lung metastasis, and liver metastasis. However, this mutation was not cooperative with MDM2 overexpression in experimental assays for transformation or growth. Nevertheless, MDM2 and PIK3CA are genes worthy of further investigation in patients with sclerosing rhabdomyosarcoma and might be considered in the enrollment of these patients into clinical trials of targeted therapeutics.