Multiplex Mutation screening by mass spectrometry: Evaluation of 820 cases from a personalized cancer medicine registry

Carol Beadling, Michael C. Heinrich, Andrea Warrick, Erin M. Forbes, Dylan Nelson, Emily Justusson, Judith Levine, Tanaya L. Neff, Janice Patterson, Ajia Presnell, Arin McKinley, Laura J. Winter, Christie Dewey, Amy Harlow, Oscar Barney, Brian J. Druker, Kathryn G. Schuff, Christopher L. Corless

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


There is an immediate and critical need for a rapid, broad-based genotyping method that can evaluate multiple mutations simultaneously in clinical cancer specimens and identify patients most likely to benefit from targeted agents now in use or in late-stage clinical development. We have implemented a prospective genotyping approach to characterize the frequency and spectrum of mutations amenable to drug targeting present in urothelial, colorectal, endometrioid, and thyroid carcinomas and in melanoma. Cancer patients were enrolled in a Personalized Cancer Medicine Registry that houses both clinical information and genotyping data, and mutation screening was performed using a multiplexed assay panel with mass spectrometry-based analysis to detect 390 mutations across 30 cancer genes. Formalin fixed, paraffin-embedded specimens were evaluated from 820 Registry patients. The genes most frequently mutated across multiple cancer types were BRAF, PIK3CA, KRAS, and NRAS. Less common mutations were also observed in AKT1, CTNNB1, FGFR2, FGFR3, GNAQ, HRAS, and MAP2K1. Notably, 48 of 77 PIK3CA-mutant cases (62%) harbored at least one additional mutation in another gene, most often KRAS. Among melanomas, only 54 of 73 BRAF mutations (74%) were the V600E substitution. These findings demonstrate the diversity and complexity of mutations in druggable targets among the different cancer types and underscore the need for a broad-spectrum, prospective genotyping approach to personalized cancer medicine.

Original languageEnglish (US)
Pages (from-to)504-513
Number of pages10
JournalJournal of Molecular Diagnostics
Issue number5
StatePublished - Sep 2011

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Medicine


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