MDM2 amplification and PI3KCA mutation in a case of sclerosing rhabdomyosarcoma

Ken Kikuchi, George R. Wettach, Christopher Ryan, Arthur Hung, Jody E. Hooper, Carol Beadling, Andrea Warrick, Christopher Corless, Susan Olson, Charles Keller, Atiya Mansoor

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article number520858
JournalSarcoma
Volume2013
DOIs
StatePublished - 2013

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Rhabdomyosarcoma
Mutation
Neoplasm Metastasis
Lung
Polyploidy
Gene Amplification
Cytogenetic Analysis
Neoplasm Genes
Subcutaneous Tissue
Growth
Fluorescence In Situ Hybridization
Cytogenetics
Foot
Autopsy
Exons
Mass Spectrometry
Neoplasms
Clone Cells
Fibroblasts
Clinical Trials

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

MDM2 amplification and PI3KCA mutation in a case of sclerosing rhabdomyosarcoma. / Kikuchi, Ken; Wettach, George R.; Ryan, Christopher; Hung, Arthur; Hooper, Jody E.; Beadling, Carol; Warrick, Andrea; Corless, Christopher; Olson, Susan; Keller, Charles; Mansoor, Atiya.

In: Sarcoma, Vol. 2013, 520858, 2013.

Research output: Contribution to journalArticle

Kikuchi, Ken ; Wettach, George R. ; Ryan, Christopher ; Hung, Arthur ; Hooper, Jody E. ; Beadling, Carol ; Warrick, Andrea ; Corless, Christopher ; Olson, Susan ; Keller, Charles ; Mansoor, Atiya. / MDM2 amplification and PI3KCA mutation in a case of sclerosing rhabdomyosarcoma. In: Sarcoma. 2013 ; Vol. 2013.
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AU - Corless, Christopher

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