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E. Bitter
Author of
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-076 - MAP2K1 Mutations in NSCLC: Clinical Presentation and Co-Occurrence of Additional Genetic Aberrations (ID 5885)
14:30 - 14:30 | Author(s): E. Bitter
- Abstract
Background:
The clinical impact of somatic MAP2K1 mutations remain uncertain in non-small cell lung cancer (NSCLC). Activation of the MEK1-cascade might play a central role in resistance to targeted BRAF V600E, EML4-ALK and EGFR T790M inhibition, but so far, only MAP2K1 K57N could be identified and linked functionally for this target. Clinical trials combining specific inhibitors for predefined NSCLC subgroups with MEK inhibitors are continuous. We performed this study to characterize MAP2K1-mutated NSCLC clinically and molecularly.
Methods:
Tumor tissue collected consecutively from 4590 NSCLC patients within a molecular screening network between 07/2014 and 07/2015 was analyzed for MAP2K1 mutations using next-generation sequencing (NGS) with a set of 102 amplicons in 14 genes. Clinical and molecular characteristics of these patients are described and compared with an internal control group of NSCLC patients and an independent control Group of The Cancer Genome Atlas (TCGA).
Results:
We classified 20 (0,4%) patients with MAP2K1 mutations. They were frequently found in adenocarcinoma (n=19) and were expressively associated with smoking. The most common MAP2K1 mutation was K57N. The majority of patients (n=15) had additional oncogenic driver aberrations, including mutations in ALK, EGFR or BRAF, and MET amplification. TP53 mutations are found in 11 patients. In 5 patients (25.0%) MAP2K1 occured exclusively. TCGA analysis reveals additional 14 patients with MAP2K1 mutations, whereof 11 have additional TP53 mutations and two have KRAS mutations. The majority of patients in our cohort has stage IV NSCLC, all patients in TCGA receive surgery for localized stages.
Conclusion:
This analysis displays that MAP2K1 mutations might occur at any stage of NSCLC and can be associated with targetable aberrations in smoking stage IV patients. Combination of targeted therapy against the known driver aberrations with MEK inhibitors might be an hopeful therapeutic outlook in the near future.
