Low-depth whole genome sequencing reveals copy number variations associated with higher pathologic grading and more aggressive subtypes of lung non-mucinous adenocarcinoma.

Objective: Histology grade, subtypes and TNM stage of lung adenocarcinomas are useful predictors of prognosis and survival. The aim of the study was to investigate the relationship between chromosomal instability, morphological subtypes and the grading system used in lung non-mucinous adenocarcinoma (LNMA). Methods: We developed a whole genome copy number variation (WGCNV) scoring system and applied next generation sequencing to evaluate CNVs present in 91 LNMA tumor samples. Results: Higher histological grades, aggressive subtypes and more advanced TNM staging were associated with an increased WGCNV score, particularly in CNV regions enriched for tumor suppressor genes and oncogenes. In addition, we demonstrate that 24-chromosome CNV profiling can be performed reliably from specific cell types (<100 cells) isolated by sample laser capture microdissection. Conclusions: Our findings suggest that the WGCNV scoring system we developed may have potential value as an adjunct test for predicting the prognosis of patients diagnosed with LNMA.