1. K-ras Mutation Subtypes in NSCLC and Associated Co-occuring Mutations in Other Oncogenic Pathways 
Matthias Scheffler, MD, Michaela A. Ihle, PhD, Rebecca Hein, PhD, Sabine Merkelbach-Bruse, PhD, Andreas H. Scheel, MD, Janna Siemanowski, PhD, Johannes Brägelmann, MD, Anna Kron, MSc, Nima Abedpour, PhD, Frank Ueckeroth, MSc, Merle Schüller, Sophia Koleczko, MD, Sebastian Michels, MD, Jana Fassunke, PhD, Helen Pasternack, PhD, Carina Heydt, PhD, Monika Serke, MD, Rieke Fischer, MD, Wolfgang Schulte, MD, Ulrich Gerigk, MD, Lucia Nogova, MD, MSc, Yon-Dschun Ko, MD, Diana S.Y. Abdulla, MD, Richard Riedel, MD, Karl-Otto Kambartel, MD, Joachim Lorenz, MD, Imke Sauerland, MD, Winfried Randerath, MD, Britta Kaminsky, MD, Lars Hagmeyer, MD, Christian Grohé, MD, Anna Eisert, MD, Rieke Frank, MD, Leonie Gogl, Carsten Schaepers, Alessandra Holzem, Martin Hellmich, PhD, Roman K. Thomas, MD, PhD, Martin Peifer, PhD, Martin L. Sos, MD, PhD, Reinhard Büttner, MD, PhD, Jürgen Wolf, MD, PhD 
Journal of Thoracic Oncology 
Volume 14, Issue 4, Pages (April 2019)
DOI: /j.jtho
Copyright © 2019 International Association for the Study of Lung Cancer Terms and Conditions

2. Figure 1
(A) Analytical workflow of this study. (B) Pie chart visualizing the relative frequencies of different KRAS mutation subtypes among the cohort. (C) Frequency of co-occurring aberrations in KRAS-mutated patients (inrelation to the numbers analyzed). Only prevalences of at least 5% are shown. AKT1, AKT/serine threonine kinase 1 gene; ALK, ALK receptor tyrosine kinase gene; amp, amplification; ATM, ATM serine/threonine kinase gene; CI, confidence interval; CTNNB1, catenin beta 1 gene; DDR2, discoidin domain receptor tyrosine kinase 2 gene; ERBB2, erb-b2 receptor tyrosine kinase 2 gene; ERBB4, erb-b2 receptor tyrosine kinase 4 gene; FGFR1, fibroblast growth factor receptor 1 gene; FGFR2, fibroblast growth factor receptor 2 gene; FISH, fluorescence in situ hybridization; HER2, synonym of ERBB2; KDR, kinase insert domain receptor gene; KEAP1, kelch like ECH associated protein 1 gene; KIT, KIT proto-oncogene receptor tyrosine kinase gene; MAP2K1, mitogen-activated protein kinase kinase 1 gene; MET, MNNG HOST Transforming gene; mut, mutation; NFE2L2, nuclear factor erythroid 2, like 2 gene; NGS, next-generation sequencing; PDGFR, previous symbol of PDGFRB (platelet derived growth factor receptor beta gene); PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene; PIK3CG, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma gene; PTEN, phosphatase and tensin homolog gene; RET, ret proto-oncogene gene; SMARCA4, SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 gene; STK11, serine/threonine kinase 11 gene; TP53, tumor protein p53 gene.
Journal of Thoracic Oncology  , DOI: ( /j.jtho )
Copyright © 2019 International Association for the Study of Lung Cancer Terms and Conditions

3. Figure 2
(A) Heatmap visualizing the relative frequencies of additional aberrations in the most common subtypes of KRAS mutations as compared with the average appearances of the whole cohort. Only aberrations with a frequency of higher than 1% in the total cohort were considered. (B) Association of different KRAS mutation subtypes with specific co-mutations and significance of co-occurrence as compared with in the total cohort. ERBB2amp, erb-b2 receptor tyrosine kinase 2 gene amplification; ERBB4mut, erb-b2 receptor tyrosine kinase 4 gene mutation; PDGFRA, platelet derived growth factor receptor alpha gene; PTEN, phosphatase and tensin homolog gene.
Journal of Thoracic Oncology  , DOI: ( /j.jtho )
Copyright © 2019 International Association for the Study of Lung Cancer Terms and Conditions

4. Figure 3
(A) Overall survival of the survival analysis cohort (n = 609) depending on the Union for International Cancer Control stages. (B) Overall survival of patients with metastasis (Union for International Cancer Control stage IV) depending on the underlying KRAS mutation (n = 375). (C) Overall survival of stage IV patients with and without additional mutations according to the panel used for reevaluation. (D) Overall survival of stage IV patients with and without co-occurring serine/threonine kinase 11 gene (STK11) mutations.
Journal of Thoracic Oncology  , DOI: ( /j.jtho )
Copyright © 2019 International Association for the Study of Lung Cancer Terms and Conditions

5. Figure 4
Reconstructed subclonal populations of whole exome sequenced KRAS and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA)-mutated samples. Cancer cell fractions indicate the diverse clonality status of the driver mutations. (A) In sample C , the KRAS mutation (G12C) was clonal, whereas the PIK3CA E545K mutation was subclonal. This case had a total of 1197 mutations, but 90.2% of these mutations were subclonal. A tumor protein p53 gene (TP53) mutation (R248L) together with subclonal loss was detected in a minor subclone, thus showing a biallelic deactivation of TP53 in about 59% of the tumor cells. (B) In C , the KRAS Q61L mutation was present in the same subclonal population that harbors the PIK3CA mutation (E545K).
Journal of Thoracic Oncology  , DOI: ( /j.jtho )
Copyright © 2019 International Association for the Study of Lung Cancer Terms and Conditions