2024 Targeted Therapies for Lung Cancer (TTLC) - Abstracts & Posters-PP01.05 Repetto

PP01.05 Repetto - Poster

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The document analyzes MYC gene amplifications in lung adenocarcinoma (LUAD) to understand MYC-dependency. Through the analysis of 68,920 tumor samples, MYC amplification was found in 8% of LUAD cases. These amplifications varied in size and type, with some occurring on extrachromosomal DNA (ecDNA). The study revealed that MYC amplifications often occur without other driver alterations and can lead to acquired resistance to targeted therapies. Common concomitant events included EGFR and KRAS mutations. MYC amplifications were mutually exclusive with ROS1 fusions and MET mutations, while co-occurring with TP53 mutations and ERBB2 amplifications. Moreover, the study found different associations based on segment size, with broad MYC amplifications being mutually exclusive with ALK and ROS1 fusions, while focal amplifications co-occurred with ROS1 and ALK fusions and ALK mutations, especially in treatment-resistant samples. Overall, the analysis sheds light on the complex landscape of MYC amplifications in LUAD and their interactions with other oncogenic events, providing insights for targeted treatment strategies.

Keywords

MYC gene amplifications

lung adenocarcinoma

MYC-dependency

tumor samples

extrachromosomal DNA

acquired resistance

EGFR mutations

KRAS mutations

ROS1 fusions

TP53 mutations