Recording and classifying MET receptor mutations in cancers
- Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020 – UMR1277 - Canther – Cancer Heterogeneity, Plasticity and Resistance to Therapies, France
Figures
Figure 1
List of MET mutations found within the functional domains of the receptor.
The extracellular portion of MET consists of the SEMA domain, a PSI domain, and four immunoglobulin-plexin-transcription (IPT) repeats; the intracellular region contains the juxtamembrane domain, …
Figure 2
MET mutations leading to exon 14 skipping.
(A) Several mutations affecting the splice junctions flanking exon 14 (encoding the juxtamembrane domain) have been described in non-small cell lung cancer (NSCLC). More than 160 alterations of the …
Figure 3 with 2 supplements
Resistance mutations in the METex14Del variant after treatment with a MET TKI.
(A) Upon treatment of MET exon 14 skipping NSCLC patients with a type I MET TKI (able to bind the active form of MET kinase) or a type II MET TKI (able to bind the inactive form of MET kinase), …
Figure 3—video 1
Resistance mutations of METex14Del treated with MET TKI crizotinib.
Video of the three-dimensional crystal structure of the MET kinase domain, along with crizotinib (https://doi.org/10.2210/pdb2WGJ/pdb). Crizotinib (TKI type I) binds the active state (DFG sequence …
Figure 3—video 2
Resistance mutations of METex14Del treated with MET TKI meristinib.
Video of the three-dimensional crystal structure of the MET kinase domain, along with merestinib (https://doi.org/10.2210/pdb4EEV/pdb). Merestinib (TKI type II) binds the inactive stage (DFG-out). …
Tables
Table 1
Recording of MET mutations found in cancers (Tovar and Graveel, 2017; Ma et al., 2005; Ma et al., 2003; Liu et al., 2015; Jardim et al., 2014; Stella et al., 2011; Jagadeeswaran et al., 2006; Moon et al., 2000; Park et al., 1999; Bahcall et al., 2016).
In this table, recording the MET mutations characterized by functional studies, subdomain localization of MET mutations were indicated as well as their sensitivity to hepatocyte growth factor (HGF) …
| Domain | Subdomain | AA | Cancer | Functional assay | Sensitivity to HGF | References |
|---|---|---|---|---|---|---|
| Extracellular | SEMA | H150Y | CUP | Anchorage-independent growth assay | Stella et al., 2011 | |
| E168D | NSCLC, SCLC, BC, CUP | BaF3 cells, soft agar colony assay SCLC H446 | Ma et al., 2003 | |||
| N375S | NSCLC, SCLC, BC, CRC | Cell migration, invasion, and colony-forming assay, tumor growth study after cell xenograft | Ma et al., 2005; Jardim et al., 2014 | |||
| C385Y | CUP | Anchorage-independent growth assay | Stella et al., 2011 | |||
| M431V | Malignant pleural mesothelioma (MPM) | Cell migration and motility assay | Jagadeeswaran et al., 2006 | |||
| Juxtamembrane | R988C | NSCLC, SCLC | BaF3 cells, soft agar colony assay SCLC H446 | Ma et al., 2003; Montagne et al., 2017 | ||
| P1009S | GC | Focus formation NIH3T3 | Lee et al., 2000 | |||
| T1010I | NSCLC, SCLC, BC, CRC, CUP | Focus formation NIH3T3 | Lee et al., 2000 | |||
| Kinase N-lobe | H1086L | HPRC | Focus formation NIH3T3 | Yes | Sebai et al., 2022 | |
| P-Loop | I1102T | HPRC | Focus formation NIH3T3 | Yes | Sebai et al., 2022 | |
| P-Loop | N1118Y | Metastasis | Cell migration and invasion assay | Yes | Lorenzato et al., 2002 | |
| P-Loop | C1125G | HPRC | Focus formation NIH3T3 | Yes | Sebai et al., 2022 | |
| P-Loop | L1130S | HPRC | Focus formation NIH3T3 | Yes | Sebai et al., 2022 | |
| M1149T | HPRC/SPRC | Focus formation NIH3T3 | Yes | Jeffers et al., 1997; Michieli et al., 1999 | ||
| Kinase C-lobe | V1206L | HPRC | Focus formation NIH3T3 | Yes | Jeffers et al., 1997; Michieli et al., 1999 | |
| L1213V | SPRC | Focus formation NIH3T3 | Yes | Michieli et al., 1999 | ||
| Activation Loop (1231–1262) | V1238I | HPRC | Focus formation NIH3T3 | Yes | Jeffers et al., 1997; Michieli et al., 1999 | |
| Activation Loop (1231–1262) | D1246N/H/V | HPRC | Focus formation NIH3T3 | Yes | Jeffers et al., 1997; Michieli et al., 1999; Bahcall et al., 2016 | |
| Activation Loop (1231–1262) | Y1248C/D/H | HPRC, SPRC, OSCC, HNSCC | Focus formation NIH3T3 | Yes | Jeffers et al., 1997; Michieli et al., 1999 | |
| Activation Loop (1231–1262) | Y1253D | OSCC, HNSCC, BC | Focus formation NIH3T3 | Jeffers et al., 1997; Bardelli et al., 1998; Liu et al., 2015 | ||
| COOH-terminal lobe of the kinase domain | M1268T/I | HPRC, SPRC, HCC | Focus formation NIH3T3 | Jeffers et al., 1997; Michieli et al., 1999 | ||
| V1312I | CUP | Anchorage-independent growth assay | Stella et al., 2011 |
