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(Slides)

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RET fusion (RETfus) non-small cell lung cancer (NSCLC) is a rare subtype of NSCLC found in 1-2% of cases in the USA. It can be treated with RET inhibitors, both broad and focused targeted therapies. The aim of this study was to investigate the genomic alterations (GA) in RETfus NSCLC and compare them with RETfus- NSCLC.<br /><br />The study analyzed data from RETfus NSCLC cases obtained from archival specimens. These specimens underwent comprehensive genomic profiling (CGP) using hybrid capture-based sequencing and assessment of various GA, including base substitutions, insertions and deletions, rearrangements, and copy number changes. The study also calculated tumor mutational burden (TMB) and analyzed PD-L1 expression.<br /><br />A total of 424 cases of RETfus NSCLC were identified among 57,252 NSCLC specimens. The RETfus cases were found to be younger and had lower GA/tumor compared to RETfus- cases. They also had a lower chance of having a high genome-wide loss-of-heterozygosity score, lower TMB, and lower tobacco genomic signature. However, they had a higher APOBEC signature, indicating a different mutational profile.<br /><br />Histologically, RETfus NSCLC specimens were subclassified into various subtypes, with high grade solid non-acinar as the most common subtype. There were no significant differences in GA among the histologic subtypes.<br /><br />The study concludes that RETfus NSCLC has a unique distribution of genetic biomarkers and histologic subtypes. With the recent approval of more specific RET kinase targeting inhibitors, further study of RETfusion NSCLC histology and genomic/biomarker status is warranted.<br /><br />It is important to note that the study has limitations, including the lack of prospective clinical and survival data and an unequal distribution between the RETfus and RETfus- groups.

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

RET inhibitors

targeted therapies

comprehensive genomic profiling

tumor mutational burden

PD-L1 expression

histologic subtypes