This post-hoc analysis has several limitations

minor proportion of GW 5074 patients with NSCLC have genetically profiled biopsies. Guidelines provide evidence to perform EGFR and KRAS mutation analysis in non-squamous NSCLC. We explored tumor biopsy quality offered for mutation testing, different mutations distribution, and outcome with EGFR TKI. Patient and Methods: Clinical data from 8 regional hospitals were studied for patient and tumor characteristics, treatment and overall survival. Biopsies sent to the central laboratory were evaluated for DNA quality and subsequently analyzed for mutations in exons 1821 of EGFR and exon 2 of KRAS by bidirectional sequence analysis. Results: Tumors from 442 subsequent patients were analyzed. For 74 patients tumors were unsuitable for mutation analysis. Thirty-eight patients had EGFR mutations with 79% known activating mutations. One hundred eight patients had functional KRAS mutations. The mutation spectrum was comparable to the Cosmic database. Following treatment in the first or second line with EGFR TKI median overall survival for patients with EGFR, KRAS mutations and wild type EGFR/KRAS was not reached, 20 and 9 months, respectively. Conclusion: One out of every 6 tumor samples was inadequate for mutation analysis. Patients with EGFR activating mutations treated with EGFR-TKI have the longest survival. Citation: Kerner GSMA, CTMM Air Force Consortium, Schuuring E, Sietsma J, Hiltermann TJN, et al. Common and Rare EGFR and KRAS 9057848 Mutations in a Dutch Non-Small-Cell Lung Cancer Population and Their Clinical Outcome. PLoS ONE 8: e70346. doi:10.1371/journal.pone.0070346 Editor: Surinder K. Batra, University of Nebraska Medical Center, United States of America Received March 8, 2013; Accepted June 17, 2013; Published July 29, 2013 Copyright: 2013 Kerner et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was partly funded by the CTMM Air Force consortium. CTMM pays for GSMAK’s salary and had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. No other external funding sources for this study. Competing Interests: The CTMM Air Force Consortium is a private/public consortium with involvement of academia, private companies, and the government. It is not a commercial source of funding. Gerald Kerner is funded by CTMM consortium to perform the research project that is a part of his thesis. The authors are entitled to publish all his work and share all their data publicly. No consultancy, patents, or products in development are involved. All together, this has no impact to the authors’ adherence to all the PLOS ONE policies on sharing data and materials. All authors declared not having any competing interests. E-mail: [email protected] Introduction The effect of EGFR tyrosine kinase inhibitors in patients with non-small-cell lung cancer depends on the EGFR mutation status. Therefore, selecting the adequate tumor specimen for mutational analysis is an important issue in making treatment decisions in NSCLC. In previous randomized studies comparing EGFR TKI therapy to regular chemotherapy, the proportion of patients with adequate tumor tissue for analysis ranged from 10 to 38%. Most randomized studies used different EGFR mutation tests that only examined a very 1717682 limited number of hotspot mutation