Abstract 5878: Landscape of tumor heterogeneity index and tumor mutational burden in non-small cell lung cancer

Abstract Background/Aims Tumor heterogeneity and tumor mutational burden (TMB) are novel biomarkers associated with the response to immunotherapy in non-small cell lung cancer (NSCLC), but studies report conflicting results. We aim to describe the associations between these biomarkers. Methods From records of 77 NSCLC patients, tissue next-generation sequencing (NGS) data and circulating tumor DNA (ctDNA) NGS data, along with corresponding tissue TMB (tTMB) and blood TMB (bTMB) values, were obtained. PyClone was used to estimate tumor heterogeneity from tissue sequencing data. Tumors with ≥3 clusters were defined as having high tumor heterogeneity, and those with <3 clusters as having low heterogeneity. Mutant-allele tumor heterogeneity (MATH), another estimate of tumor heterogeneity, was calculated from tissue and blood NGS data. Results Out of the 77 NSCLC cases, 21 cases had high tumor heterogeneity, and 56 cases had low tumor heterogeneity according to PyClone. High tumor heterogeneity was statistically significantly associated with higher tTMB (p-value = 0.02) but was not significantly associated with bTMB. Tumor heterogeneity was not significantly associated with age, sex, smoking status, tumor histology, or metastasis. Tumor heterogeneity was not associated with either tissue MATH (p-value = 0.86) or blood MATH (p-value = 0.30), and there was no significant association between tissue MATH and blood MATH (p-value = 0.96). There was a statistically significant positive correlation between tTMB and bTMB (r = 0.75, p < 0.001). Neither tissue MATH nor blood MATH showed significant associations with tTMB or bTMB. Conclusions High tumor heterogeneity as defined by PyClone was associated with high tTMB but not bTMB. tTMB and bTMB were strongly positively correlated. There were no evident correlations between the estimates of tumor heterogeneity. Citation Format: Jongwoo Kim, Jong Yeob Kim, Leeseul Kim, Junho Song, Liam Il-Young Chung, Young Kwang Chae. Landscape of tumor heterogeneity index and tumor mutational burden in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5878.