Profiling critical cancer gene mutations in clinical tumor samples

Laura E. MacConaill, Catarina D. Campbell, Sarah M. Kehoe, Adam J. Bass, Charles Hatton, Lili Niu, Matt Davis, Keluo Yao, Megan Hanna, Chandrani Mondal, Lauren Luongo, Caroline M. Emery, Alissa C. Baker, Juliet Philips, Deborah J. Goff, Michelangelo Fiorentino, Mark A. Rubin, Kornelia Polyak, Jennifer Chan, Yuexiang WangJonathan A. Fletcher, Sandro Santagata, Gianni Corso, Franco Roviello, Ramesh Shivdasani, Mark W. Kieran, Keith L. Ligon, Charles D. Stiles, William C. Hahn, Matthew L. Meyerson, Levi A. Garraway

Research output: Contribution to journalArticlepeer-review


Background: Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting. Methodology: We developed and implemented an optimized mutation profiling platform ("OncoMap") to interrogate ∼400 mutations in 33 known oncogenes and tumor suppressors, many of which are known to predict response or resistance to targeted therapies. The performance of OncoMap was analyzed using DNA derived from both frozen and FFPE clinical material in a diverse set of cancer types. A subsequent in-depth analysis was conducted on histologically and clinically annotated pediatric gliomas. The sensitivity and specificity of OncoMap were 93.8% and 100% in fresh frozen tissue; and 89.3% and 99.4% in FFPE-derived DNA. We detected known mutations at the expected frequencies in common cancers, as well as novel mutations in adult and pediatric cancers that are likely to predict heightened response or resistance to existing or developmental cancer therapies. OncoMap profiles also support a new molecular stratification of pediatric low-grade gliomas based on BRAF mutations that may have immediate clinical impact. Conclusions: Our results demonstrate the clinical feasibility of high-throughput mutation profiling to query a large panel of "actionable" cancer gene mutations. In the future, this type of approach may be incorporated into both cancer epidemiologic studies and clinical decision making to specify the use of many targeted anticancer agents.

Original languageEnglish
Article numbere7887
JournalPLoS One
Issue number11
Publication statusPublished - Nov 18 2009

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)


Dive into the research topics of 'Profiling critical cancer gene mutations in clinical tumor samples'. Together they form a unique fingerprint.

Cite this