Case report for an adolescent with germline RET mutation and alveolar rhabdomyosarcoma.

Cold Spring Harbor Molecular Case Studies
Kenneth A CrawfordCharles Keller

Abstract

In this case report we evaluate the genetics of and scientific basis of therapeutic options for a 14-yr-old male patient diagnosed with metastatic PAX3-FOXO1 fusion positive alveolar rhabdomyosarcoma. A distinguishing genetic feature of this patient was a germline RET C634F mutation, which is a known driver of multiple endocrine neoplasia type 2A (MEN2A) cancer. Through sequential DNA and RNA sequencing analyses over the patient's clinical course, a set of gene mutations, amplifications, and overexpressed genes were identified and biological hypotheses generated to explore the biology of RET and coexisting signaling pathways in rhabdomyosarcoma. Somatic genetic abnormalities identified include CDK4 amplification and FGFR4 G388R polymorphism. Because of the initial lack of patient-derived primary cell cultures, these hypotheses were evaluated using several approaches including western blot analysis and pharmacological evaluation with molecularly similar alveolar rhabdomyosarcoma cell lines. Once a primary cell culture became available, the RET inhibitor cabozantinib was tested but showed no appreciable efficacy in vitro, affirming with the western blot negative for RET protein expression that RET germline mutation could be only ...Continue Reading

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Citations

Mar 17, 2021·Cold Spring Harbor Molecular Case Studies·Noah E BerlowCharles Keller

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Datasets Mentioned

BETA
BYL719
AUY922
EGAS00001004359

Methods Mentioned

BETA
biopsies
biopsy
X-ray
blood draw
xenograft
nuclear translocation

Key Resources (RRID) Mentioned

CVCL_0041

Clinical Trials Mentioned

NCT01222715

Software Mentioned

CalcuSyn
EGA
Stattic
GraphPad
RMS
circos
Excel

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