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

P1.22. Whole Genome Sequencing Analysis of ALK-rearranged Non-small Cell Lung Cancer - PDF(Abstract)

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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 from 91 ALK-rearranged NSCLC cases and their matched normal tissues or blood. They also performed bulk RNA sequencing for a subset of samples. The study found that ALK expression was specifically elevated in the cancer tissues, particularly after exon 20. Genomic breakpoints on ALK were mainly found within intron 19 and were randomly distributed along the intron. The most common fusion partner gene of ALK was EML4. The study identified various variant forms of the EML4-ALK fusion, with E13;A20 being the most common. The researchers discovered 10,230 somatic structural variations (SVs) in the ALK-rearranged tumor genomes, with 83% of SVs being clustered into 395 complex genomic rearrangements. Comparisons were made between the ALK-rearranged NSCLC cohort and other NSCLC cases driven by different oncogenes. No major driver oncogenes were identified in 63 cases of ALK-rearranged NSCLC. The study also found that ALK-rearranged NSCLC showed genomic heterogeneity, challenging the previous understanding of it being a homogenous population. The researchers concluded that further investigation is needed to understand the clinical implications of this genomic heterogeneity.

Asset Subtitle

Yoon-La Choi

Meta Tag

Speaker Yoon-La Choi

Topic Pathology & Biomarkers: Genetic Biomarkers

Keywords

ALK-rearranged non-small cell lung cancer

somatic mutation landscape

whole-genome sequencing

WGS data

ALK expression

genomic breakpoints

EML4-ALK fusion

somatic structural variations

genomic rearrangements

genomic heterogeneity