Abstract 6091: Evolutionary characterisation of lung adenocarcinoma pathological subtypes in TRACERx

Background: Lung adenocarcinoma (LUAD) is a morphologically and genetically diverse disease. The prognostic impact of LUAD histological patterns have been described, such as solid growth pattern and poor outcomes, though their underlying biology is poorly understood. Furthermore, the genomic characteristics and evolutionary constraints in relation to the inter- and intra- tumoral variance of histological patterns in primary and metastatic disease are unknown. Methods: Pathological classification of 246 patients with LUAD from the TRACERx 421 cohort was performed at the whole tumor (diagnostic samples) and multi-regional sample level (matched for tumor whole exome sequencing and RNA sequencing). Circulating tumor DNA (ctDNA) data was also integrated to determine the relationship between pathological subtypes and ctDNA detection. Results: Chromosomal instability, characterized by fraction of the genome affected by subclonal copy number alterations was significantly correlated with proportion of high-grade patterns, namely solid, cribriform and micropapillary (Spearman’s Rho 0.27, p