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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
P2.03b-036 - Analysis of Potentially Targetable Mutations in 821 Patients with Squamouscell Lung Cancer Undergoing Routine NGS-Based Molecular Diagnostics (ID 5939)
14:30 - 15:45 | Author(s): R. Büttner
Molecular multiplex diagnostics is increasingly integrated now in routine diagnostics of lung adenocarcinoma (LAD). Although targetable aberrations are predominantly found in LAD, they have also been reported in squamouscell lung carcinoma (SQLC). We here present results of routine molecular multiplex diagnostics of advanced stage SQLC obtained within the German Network Genomic Medicine (NGM) and compare them with results reported previously in early stage SQLC in The Cancer Genome Atlas (TCGA) LUSC cohort.
Tumor biopsies of 821 patients consecutively diagnosed within NGM were analyzed with next-generation parallel sequencing (NGS). The panel consisted of 102 amplicons and 14 genes: KRAS, PIK3CA, BRAF, EGFR, ERBB2, NRAS, DDR2, TP53, ALK, CTNNB1, MET, AKT1, PTEN and MAP2K1. In subsets of patients, fluorescence in-situ hybridization (FISH) was performed for amplification detection of FGFR1 and MET. We queried the TCGA dataset with respect to the panel used and compared the findings. For NGM patients, therapy and outcome are also reported..
In addition to the expected frequencies of TP53, DDR2, PTEN and PIK3CA mutations, we detected EGFR mutations in 3.2% and BRAF mutations in 1.8%. Unlike the TCGA dataset, where the frequencies were 2.8% and 3.9%, respectively, the detected mutations in the NGM cohort included also activating targetable mutations (i. e., EGFR del19 and L858R, and BRAF V600E). FISH data revealed presence of MET amplification in 14.2% and of FGFR1 amplification in 20.0%. The association and correlation of these aberrations with clinical findings and prognosis as well as with PD-L1 expression status and mutational load will be presented.
Our data give an overview on the presence and clinical characteristics of targetable mutations in advanced SQLC and show, that such mutations occur in a substantial amount of patients. Thus, molecular multiplex diagnostics might be indicated also in SQLC in order to use all therapeutic options available in these patients.
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P2.03b-076 - MAP2K1 Mutations in NSCLC: Clinical Presentation and Co-Occurrence of Additional Genetic Aberrations (ID 5885)
14:30 - 15:45 | Author(s): R. Büttner
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.
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).
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.
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.
YI01b - Scientific Mentoring (ID 415)
- Event: WCLC 2016
- Type: Young Investigator Session
- Presentations: 1
YI01b.02 - Expectations from a Young Investigator (ID 6740)
09:45 - 11:45 | Author(s): R. Büttner
Expectations from a Young Investigator Over the last two decades, research has pushed lung cancer investigations from the shallows of cancer treatment to one of the most innovative positions in oncology. The improvements in molecular diagnostics, in targeted therapy and immunotherapy with the linked creeping decline of traditional chemotherapy act as a model for many other tumor entities. Joined by this paradigm shift is a demographic change to young investigators who start their career in the innovative fields of lung cancer research instead of thinking in the traditional chemotherapy-based fashion. Nevertheless, in order to detect the needs and expectations from young investigators, even the definition of "young" is hard to handle, and subjective expectations might be biased by the socioeconomic background of the investigator. We therefore set out to find a way to present more robust and reliable data on the topic. We created an online questionnaire covering age, experiences, interests, and of course needs and expectations of young investigators. The expectations focus on research topics, treatment options, mentorships and social networking. The questionnaire will be forwarded to 20 investigators in the EU, Asia, South America and the US with link to the emerging fields of lung cancer research, in order to forward it to participants who they consider young in both clinical and preclinical investigations. For subgroup analyses, we will include students with interest in this field, too. Results will be analyzed by the presenters. The poll will be open until one week of the WCLCs Young Investigator's Scientific Mentoring Session, and results of this interim analysis will be presented by this talk. Nevertheless, all participants of the WCLC 2016 are invited to answer the questionnaire during the Conference, and a final data cut will be made at December 10th, 2016. We are aware of the potential biases in online polls. A valid e-mail address and the source of the online link (i. e., who was the "supervisor") are necessary. As an incentive to participate properly, we offer all participants to be part of the "WCLC young Investigator Expectations Network (WIEN)" which will coauthor the final manuscript. As we question the expectations of how lung cancer research will work in five years, it is intended to repeat the poll in a regular manner, maybe yearly. We expect a view on the expectations from young investigators worldwide and a feeling of their needs for the future.