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Supplementary Table S1 from Functional Analysis of Somatic Mutations Affecting Receptor Tyrosine Kinase Family in Metastatic Colorectal Cancer

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posted on 2023-04-03, 16:08 authored by Leslie Duplaquet, Martin Figeac, Frédéric Leprêtre, Charline Frandemiche, Céline Villenet, Shéhérazade Sebda, Nasrin Sarafan-Vasseur, Mélanie Bénozène, Audrey Vinchent, Gautier Goormachtigh, Laurence Wicquart, Nathalie Rousseau, Ludivine Beaussire, Stéphanie Truant, Pierre Michel, Jean-Christophe Sabourin, Françoise Galateau-Sallé, Marie-Christine Copin, Gérard Zalcman, Yvan De Launoit, Véronique Fafeur, David Tulasne

Supplementary Table S1: Detailed annotation of the somatic mutations in the 58 RTKs, KRAS, PI3KCA, and TP53

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Centre National de la Recherche Scientifique

Institut Pasteur de Lille

INSERM

Cancéropôle Nord-Ouest

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ARTICLE ABSTRACT

Besides the detection of somatic receptor tyrosine kinases (RTK) mutations in tumor samples, the current challenge is to interpret their biological relevance to give patients effective targeted treatment. By high-throughput sequencing of the 58 RTK exons of healthy tissues, colorectal tumors, and hepatic metastases from 30 patients, 38 different somatic mutations in RTKs were identified. The mutations in the kinase domains and present in both tumors and metastases were reconstituted to perform an unbiased functional study. Among eight variants found in seven RTKs (EPHA4-Met726Ile, EPHB2-Val621Ile, ERBB4-Thr731Met, FGFR4-Ala585Thr, VEGFR3-Leu1014Phe, KIT-Pro875Leu, TRKB-Leu584Val, and NTRK2-Lys618Thr), none displayed significantly increased tyrosine kinase activity. Consistently, none of them induced transformation of NIH3T3 fibroblasts. On the contrary, two RTK variants (FGFR4-Ala585Thr and FLT4-Leu1014Phe) caused drastic inhibition of their kinase activity. These findings indicate that these RTK variants are not suitable targets and highlight the importance of functional studies to validate RTK mutations as potential therapeutic targets.

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    Molecular Cancer Therapeutics

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