2024 World Conference on Lung Cancer (WCLC) - Posters-P3.06D.09 Reciprocal DNA Fusions and their Association with DNA Damage Response Genes in Patients with NSCLC Through cfDNA NGS

P3.06D.09 Reciprocal DNA Fusions and their Association with DNA Damage Response Genes in Patients with NSCLC Through cfDNA NGS

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This study investigates the prevalence and patterns of reciprocal DNA fusions and their association with DNA damage response (DDR) genes in patients with non-small cell lung cancer (NSCLC) using next-generation sequencing (NGS) of circulating cell-free DNA (cfDNA). The cohort comprised 2,385 advanced-stage NSCLC patients analyzed over a six-year period (October 2016 - September 2022). The primary aim was to evaluate the occurrence of specific gene rearrangements, primarily ALK, RET, and ROS1, and their co-mutations with DDR-related genes.<br /><br />The findings indicate that ALK rearrangements were the most prevalent (63.4%), followed by RET (25.3%) and ROS1 (11.3%). A small subset, about 6%, showed reciprocal fusions only. Common across all groups were mutations in TP53, present in about 42-68% of cases, while other DDR gene mutations like ATM and ARID1A showed variable presence, ranging from 0-20%.<br /><br />Both activating and reciprocal fusion events were evaluated, with differences noted in co-mutation patterns, particularly with ATM and ARID1A, among the various types of reciprocal rearrangements. The demographic analysis showed a near-equal male-female distribution, with a median age of 60 years. Adenocarcinoma (ADC) was the prominent histological subtype across all rearrangement types.<br /><br />This research underscores the complexity of rearrangement types and their potential to guide the use of targeted therapies, such as Tyrosine Kinase Inhibitors (TKIs) tailored to specific oncogenic drivers like ALK, RET, and ROS1. Additionally, the study highlights the significant role of TP53 and its prevalence in patients with these rearrangements, suggesting possible implications for treatment strategies targeting the repair of DNA damage. The use of NGS on cfDNA offers a minimally invasive approach to detect such genetic alterations, crucial in devising patient-specific therapeutic strategies.

Asset Subtitle

Laila Roisman

Meta Tag

Speaker Laila Roisman

Topic Pathology & Biomarkers

Keywords

reciprocal DNA fusions

DNA damage response

non-small cell lung cancer

next-generation sequencing

circulating cell-free DNA

ALK rearrangements

RET rearrangements

ROS1 rearrangements

TP53 mutations

Tyrosine Kinase Inhibitors