2023 World Conference on Lung Cancer (Posters)-P1.22. RET Fusion (RETfus+) Driven Non-Small Cell Lung Cancer (NSCLC): AComprehensive Genomic Profiling (CGP) Study with Histologic Correlation

P1.22. RET Fusion (RETfus+) Driven Non-Small Cell Lung Cancer (NSCLC): AComprehensive Genomic Profiling (CGP) Study with Histologic Correlation - PDF(Abstract)

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The study presented at the WCLC 2023 conference focused on RET fusion (RETfus) driven non-small cell lung cancer (NSCLC) and aimed to describe the genomic alterations and histologic characteristics of this subtype. RETfus status is found in 1-2% of NSCLC cases and can be treated with targeted therapies using RET inhibitors. <br /><br />The retrospective analysis included 424 NSCLC cases with RET fusion, which were evaluated for genomic alterations using comprehensive genomic profiling (CGP) and histologic correlation. The results showed that RETfus cases were younger, more often female, and had lower genomic alterations per tumor compared to non-RETfus NSCLC cases. <br /><br />Furthermore, the study found that 5% of RETfus NSCLC cases had activating EGFR short variant mutations, indicating acquired resistance mutations. RETfus cases had a lower chance of having a high genome-wide loss-of-heterozygosity score and a lower tumor mutational burden. The tobacco genomic signature was lower, while the APOBEC signature was higher in RETfus cases. <br /><br />Histologically, RETfus NSCLC specimens were classified into various subtypes, with no significant differences in genomic alterations among them. However, RETfus NSCLC differed significantly from non-RETfus NSCLC in terms of histologic subtypes, genomic signatures, and biomarkers. <br /><br />The authors concluded that RETfus NSCLC has a unique distribution of histologic subtypes and genomic alterations, suggesting that tumor biology is driven by the RET fusion rather than histology. With the approval of specific RET inhibitors in the pan-cancer treatment setting, further studies analyzing RET fusion NSCLC are warranted.

Asset Subtitle

Alina Basnet

Meta Tag

Speaker Alina Basnet

Topic Pathology & Biomarkers: Genetic Biomarkers

Keywords

RET fusion

non-small cell lung cancer

NSCLC

genomic alterations

histologic characteristics

targeted therapies

RET inhibitors

comprehensive genomic profiling

activating EGFR short variant mutations

acquired resistance mutations