Potential pitfalls of mass spectrometry to uncover mutations in childhood soft tissue sarcoma: A report from the Children’s Oncology Group View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-12

AUTHORS

Lin Xu, Raphael A Wilson, Theodore W Laetsch, Dwight Oliver, Sheri L Spunt, Douglas S Hawkins, Stephen X Skapek

ABSTRACT

Mass spectrometry-based methods have been widely applied - often as the sole method - to detect mutations in human cancer specimens. We applied this approach to 52 childhood soft tissue sarcoma specimens in an attempt to identify potentially actionable mutations. This analysis revealed that 25% of the specimens harbored high-confidence calls for mutated alleles, including a mutation encoding FLT3(I836M) that was called in four cases. Given the surprisingly high frequency and unusual nature of some of the mutant alleles, we carried out ultra-deep next generation sequencing to confirm them. We confirmed only three mutations, which encoded NRAS(A18T), JAK3(V722I) and MET(R970C) in three specimens. Beyond highlighting those mutations, our findings demonstrate potential pitfalls of primarily utilizing a mass spectrometry-based approach to broadly screen for DNA sequence variants in archived, clinical-grade tumor specimens. Duplicate mass spectrometric analyses and confirmatory next generation sequencing can help diminish false positive calls, but this does not ameliorate potential false negatives due in part to evaluating a limited panel of sequence variants. More... »

PAGES

33429

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep33429

DOI

http://dx.doi.org/10.1038/srep33429

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1006884483

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27642091


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