2023 World Conference on Lung Cancer (Posters)-P1.22. Whole Genome Sequencing Analysis of ALK-rearranged Non-small Cell Lung Cancer

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This study aimed to characterize the somatic mutation landscape of ALK-rearranged non-small cell lung cancer (NSCLC) using whole-genome sequencing (WGS). The researchers collected WGS data of 91 ALK-rearranged NSCLC cases, including 64 newly sequenced and 27 publicly available cases. Additionally, bulk RNA sequencing was performed for a subset of the samples.<br /><br />The study revealed the genomic heterogeneity of ALK-rearranged NSCLC, which was previously considered a homogenous population. The clinical implications of this heterogeneity require further investigation. The majority of the NSCLC cases in the cohort were adenocarcinomas, with 34% of patients diagnosed before the age of 50. The fusion partner genes of ALK were predominantly EML4.<br /><br />The classification of ALK rearrangements showed that simple rearrangements accounted for a smaller proportion compared to complex rearrangements, including chromothripsis. The study also compared the mutation burdens of NSCLC cases driven by other oncogenes, such as EGFR and KRAS mutations.<br /><br />Interestingly, the ALK-rearranged NSCLC cases included ever-smokers, but their tumor genomes had only a small number of smoking-induced mutations. There was also a correlation between smoking-induced mutation burden and the distance between tumor mass and trachea.<br /><br />The study categorized NSCLCs driven by ALK and other oncogenes based on their predicted cell type of origin, with alveolar type 2 cells identified as the cell of origin for ALK-driven NSCLCs.<br /><br />In conclusion, this study provided a comprehensive somatic mutation landscape of ALK-rearranged NSCLC at the whole-genome level. The findings highlighted the genomic heterogeneity of ALK-rearranged NSCLC and suggested the need for further investigation of its clinical implications.

Asset Subtitle

Yoon-La Choi

Meta Tag

Speaker Yoon-La Choi

Topic Pathology & Biomarkers: Genetic Biomarkers

Keywords

somatic mutation landscape

ALK-rearranged

NSCLC

whole-genome sequencing

genomic heterogeneity

adenocarcinomas

fusion partner genes

chromothripsis

mutation burdens

cell type of origin