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Publication — IRIC

Targeted Mass Spectrometry Analyses of Somatic Mutations in Colorectal Cancer Specimens Using Differential Ion Mobility.

Identification of K-Ras and B-Raf mutations in colorectal cancer (CRC) is essential to predict patients’ response to anti-EGFR therapy and formulate appropriate therapeutic strategies to improve prognosis and survival. Here, we combined parallel reaction monitoring (PRM) with high-field asymmetric waveform ion mobility (FAIMS) to enhance mass spectrometry sensitivity and improve the identification of low-abundance K-Ras and B-Raf mutations in biological samples without immunoaffinity enrichment. In targeted LC-MS/MS analyses, FAIMS reduced the occurrence of interfering ions and enhanced precursor ion purity, resulting in a 3-fold improvement in the detection limit for K-Ras and B-Raf mutated peptides. In addition, the ion mobility separation of isomeric peptides using FAIMS facilitated the unambiguous identification of K-Ras G12D and G13D peptides. The application of targeted LC-MS/MS analyses using FAIMS is demonstrated for the detection and quantitation of B-Raf V600E, K-Ras G12D, G13D, and G12V in CRC cell lines and primary specimens.

Publication date
December 28, 2023
Principal Investigators
Wu Z, Bonneil E, Belford M, Boeser C, Dunyach JJ, Thibault P
PubMed reference
J Proteome Res 2023
PubMed ID
38153093
Affiliation
Institute for Research in Immunology and Cancer (IRIC) Université de Montréal, Montréal H3T 1J4, Canada.