Abstract 471: Tumor clonal status predicts clinical outcomes of non-small-cell lung cancer

Background: Intratumoral heterogeneity is a major cause of resistance to therapeutic agents and treatment failure. In this study, we evaluated clonal status, which reflects intratumoral heterogeneity, in non-small-cell lung cancer (NSCLC) and we discussed its clinical implications. Materials and Methods: Targeted sequencing was performed using a customized panel comprising 70 solid tumor-associated genes on samples obtained from 99 lung adenocarcinoma cases. In parallel, TCGA-LUAD cases with clinical information were extracted from the GDC data portal for validation. Clonal status was identified from the allele frequency of the mutated gene using the Maftools package. Results: We found no significant relationships with stage between the total number of mutations or the number of variants when classified according to the variant effect predictor. There was a positive correlation between the maximum primary tumor diameter and the number of clones (σ=0.2318, P-value = 0.0339). Additionally, the number of clones increased with stage (p-value= 0.0220, Kruskal-Wallis chi-squared test). Disease-free survival (DFS) was significantly shorter among cases wherein tumors comprised two or more clones than among cases in which tumors were comprised of only one clone (P-value = 0.008, Log-rank test). A multivariate model that controlled for total number of mutations, tumor stage, sex, age, and smoking indicated that the number of clones was an independent determinant of DFS. Conclusions: Number of clones comprising the primary lesion was positively correlated with tumor size and stage, and was an independent factor affecting clinical outcome, indicating that a description of tumor clonality may be required for next-generation sequencing. Citation Format: Eun Young Kim, Sanghoon Lee, Arum Kim, Tae Hee Kim, Yoon Soo Chang. Tumor clonal status predicts clinical outcomes of non-small-cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 471.