| First Author | Lu X | Year | 2017 |
| Journal | Cancer Res | Volume | 77 |
| Issue | 16 | Pages | 4498-4505 |
| PubMed ID | 28522754 | Mgi Jnum | J:243113 |
| Mgi Id | MGI:5907743 | Doi | 10.1158/0008-5472.CAN-16-1944 |
| Citation | Lu X, et al. (2017) MET Exon 14 Mutation Encodes an Actionable Therapeutic Target in Lung Adenocarcinoma. Cancer Res 77(16):4498-4505 |
| abstractText | Targeting somatically activated oncogenes has revolutionized the treatment of non-small cell lung cancer (NSCLC). Mutations in the gene mesenchymal-epithelial transition (MET) near the exon 14 splice sites are recurrent in lung adenocarcinoma and cause exon skipping (METDelta14). Here, we analyzed 4,422 samples from 12 different malignancies to estimate the rate of said exon skipping. METDelta14 mutation and transcript were most common in lung adenocarcinoma. Endogenously expressed levels of METDelta14 transformed human epithelial lung cells in a hepatocyte growth factor-dependent manner. In addition, overexpression of the orthologous mouse allele induced lung adenocarcinoma in a novel, immunocompetent mouse model. Met inhibition showed clinical benefit in this model. In addition, we observed a clinical response to crizotinib in a patient with METDelta14-driven NSCLC, only to observe new missense mutations in the MET activation loop, critical for binding to crizotinib, upon clinical progression. These findings support genomically selected clinical trials directed toward METDelta14 in a fraction of NSCLC patients, confirm second-site mutations for further therapeutic targeting prior to and beyond acquired resistance, and provide an in vivo system for the study of METDelta14 in an immunocompetent host. Cancer Res; 77(16); 4498-505. (c)2017 AACR. |
