Journal
ANNALS OF ONCOLOGY
Volume 24, Issue 5, Pages 1319-1325Publisher
OXFORD UNIV PRESS
DOI: 10.1093/annonc/mds626
Keywords
eML4-ALK; lung cancer; mEK1; mutation; pIK3CA
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Funding
- National Natural Science Foundation of China [81172251]
- Fund for Innovative Research Team of Zhejiang Education Department [T200907]
- Qianjiang Scholar Professorship program, Zhejiang Province, China
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Background: Oncogenic driver mutations are responsible for the initiation and maintenance of non-small-cell lung cancer (NSCLC). Elucidation of driver mutation occurrence in NSCLC has important clinical implications. Patients and methods: NSCLC at various clinical stages were studied for their oncogenic mutations and their association with patients' disease-free survival (DFS). Results: Of 488 patients with NSCLC, 28 had EML4-ALK fusions. Female, young age (<60 years old), and nonsmoker patients had significant greater mutation frequencies than male, old age (>= 60 years old), and smoker patients, respectively (P<0.05). Of 392 patients with NSCLC, 13 had PIK3CA mutations and 3 had MEK1 mutations. EML4-ALK, PIK3CA, and MEK1 mutations were mutually exclusive. EML4-ALK fusion was found to be of coexistence with EGFR and KRAS mutations in two cases. In stage IA NSCLC, EML4-ALK-positive patients had longer DFS than EML4-ALK-negative patients (P=0.04). However, in stage IIIA NSCLC, EML4-ALK-positive patients had poorer DFS than EML4-ALK-negative patients (P<0.01). Moreover, multivariate analysis indicated that in stage IIIA NSCLC EML4-ALK fusion was the only significant indicator for poor DFS (P<0.001). Furthermore, tumors with EML4-ALK fusions had significantly higher levels of ERCC1, a molecule with a key role in platinum drug efficacy, than tumors without EML4-ALK fusions. Conclusion: EML4-ALK, PIK3CA, and MEK1 mutations occurred in NSCLC with various distinct clinicopathological characteristics. EML4-ALK fusions could serve as a significant prognostic indicator for locally advanced NSCLC.
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