Title :

Functional Analysis of Somatic Mutations Affecting Receptor Tyrosine Kinase Family in Metastatic Colorectal Cancer

Author(s) :

Duplaquet, Leslie [Auteur]
Figeac, Martin [Auteur]
Leprêtre, Frédéric [Auteur]
Frandemiche, Charline [Auteur]
Villenet, Céline [Auteur]
Sebda, Shéhérazade [Auteur]
Sarafan-Vasseur, Nasrin [Auteur]
Bénozène, Mélanie [Auteur]
Vinchent, Audrey [Auteur]
Goormachtigh, Gautier [Auteur]
Wicquart, Laurence [Auteur]
Rousseau, Nathalie [Auteur]
Beaussire, Ludivine [Auteur]
Truant, Stéphanie [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Michel, Pierre [Auteur]
Sabourin, Jean-Christophe [Auteur]
Galateau-Sallé, Françoise [Auteur]
Copin, Marie-Christine [Auteur]
Zalcman, Gérard [Auteur]
De Launoit, Yvan [Auteur]
Fafeur, Véronique [Auteur]
Tulasne, David [Auteur]

Journal title :

MOLECULAR CANCER THERAPEUTICS

Pages :

1137-1148

Publisher :

American Association for Cancer Research

Publication date :

2019-06-01

ISSN :

1535-7163

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL