2025 Targeted Therapies of Lung Cancer (TTLC) - Posters-PP01.38 High Frequency of Actionable Driver Alterations in Lung Cancer Patients with Germline MUTYH Mutations: A Retrospective Analysis

PP01.38 High Frequency of Actionable Driver Alterations in Lung Cancer Patients with Germline MUTYH Mutations: A Retrospective Analysis

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This retrospective study, conducted by researchers from the University of California at Irvine, investigates the prevalence of actionable driver mutations in lung cancer patients with germline MUTYH mutations (gMUTYHm). The focus was on patients whose plasma samples exhibited a variant allele frequency (VAF) for gMUTYHm between 45% and 55%, as identified through next-generation sequencing from January 2021 to October 2024.<br /><br />MUTYH is a gene crucial for repairing oxidative DNA damage through the base excision repair pathway. Biallelic germline mutations in MUTYH are linked to an inherited cancer syndrome leading to colorectal cancer. However, the full impact and implications of possessing a single gMUTYHm on the risk of solid tumors, including lung cancer, remain unclear.<br /><br />In total, 12 lung cancer patients were identified with gMUTYHm, with a median age of 66, and a slight male predominance. Notably, 67% of these patients had adenocarcinoma, and 67% had brain metastases. A high frequency of actionable mutations was observed, with 8 out of 12 patients having such mutations. Specifically, all patients with adenocarcinoma featured actionable driver mutations: EGFR mutations were most common, followed by EML4-ALK fusions and BRAF V600E mutations.<br /><br />This study highlights a potential link between gMUTYHm and targetable mutations in non-small cell lung cancer (NSCLC), particularly adenocarcinoma. The findings suggest that individuals with gMUTYHm might possess a greater propensity for developing lung adenocarcinomas with actionable driver mutations, underscoring the need for further research to elucidate the relationship and explore the potential benefits of targeted therapy in managing such cases.

Asset Subtitle

Zhaohui Arter

Keywords

lung cancer

germline MUTYH mutations

actionable driver mutations

adenocarcinoma

next-generation sequencing

EGFR mutations

EML4-ALK fusions

BRAF V600E mutations

non-small cell lung cancer

targeted therapy