Nicholas T. Gimbrone, BS, Bhaswati Sarcar, PhD, Edna R

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Somatic Mutations and Ancestry Markers in Hispanic Lung Cancer Patients Nicholas T. Gimbrone, BS, Bhaswati Sarcar, PhD, Edna R. Gordian, MA, Jason I. Rivera, BS, Christian Lopez, BS, Sean J. Yoder, MS, Jamie K. Teer, PhD, Eric A. Welsh, PhD, Alberto A. Chiappori, MD, Matthew B. Schabath, PhD, Gary W. Reuther, PhD, Julie Dutil, PhD, Miosotis Garcia, MD, Ronald Ventosilla-Villanueva, MD, Luis Vera-Valdivia, MD, Alejandro Yabar-Berrocal, MD, Rodrigo Motta-Guerrero, MD, Pedro G. Santiago-Cardona, PhD, Teresita Muñoz-Antonia, PhD, W. Douglas Cress, PhD Journal of Thoracic Oncology Volume 12, Issue 12, Pages 1851-1856 (December 2017) DOI: 10.1016/j.jtho.2017.08.019 Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Mutation frequency comparisons using Fisher’s exact test. (A) Mutation rate comparison between 75 lung adenocarcinomas in H/L patients and 748 in NHW patients. Histograms of the four most common mutations in adenocarcinomas in NHW patients as indicated as the percentage of patients with any detected variant. Number of mutants or number in cohort is indicated above the histograms. All significantly different rates are indicated by Fisher’s exact test p values: *p <0.05, **p <0.01, and ***p <0.001. See Supplementary Table 2 for analysis of additional genes. (B) Mutation rate comparison between male and female patients and H/L and NHW patients. Same analysis as in (A), except that H/L and NHW patients were divided into male and female patients. See Supplementary Table 3 for p values. (C) Mutation rate comparison between H/L (and NHW) ever-smokers and never-smokers. Although statistically insignificant, the trend suggests that EGFR mutations are seen more commonly in nonsmokers, whereas KRAS and seronine/threonine kinase 11 gene (STK11) mutations are more frequently seen in smokers. See Supplementary Table 4 for p values. (D) Mutation rate comparison between H/L male and female patients and ever-smokers and never-smokers. Although statistically insignificant, the trend suggests that EGFR mutations are seen more commonly in nonsmokers, whereas KRAS and STK11 mutations are more frequently mutated in smokers. See Supplementary Table 5 for p values. (E) Mutation rate comparison between NHW males and female patients and ever-smokers and never-smokers. See Supplementary Table 6 for p values. TP53, tumor protein p53 gene. Journal of Thoracic Oncology 2017 12, 1851-1856DOI: (10.1016/j.jtho.2017.08.019) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Mutation rate comparison by ancestry. (A) The Ward linkage method and Euclidean distance metric were used to cluster H/L patients by ancestry. The clusters were classified as follows: (1) indigenous American (green cluster), (2) African (red and left blue clusters), and (3) European (right blue cluster). (B) Mutation rate comparison between the three ancestral clusters. Mutation rates of four common drivers within the three ancestral clusters reveal a statistically significant difference between tumor protein p53 gene (TP53) mutations between indigenous American and European (p = 0.0087) and indigenous American and African ancestral clusters (p = 0.011). The same comparison for EGFR has p values of 0.058 and 0.072, respectively. See Supplementary Table 7 for p values. seronine/threonine kinase 11 gene. Journal of Thoracic Oncology 2017 12, 1851-1856DOI: (10.1016/j.jtho.2017.08.019) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions