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BACKGROUND: Primary lung carcinomas are extremely rare in childhood, resulting in limited knowledge of their biology and potential therapeutic targets. METHODS: Whole genome sequencing analysis was performed on 14 patients, thereof 13 pediatric patients. The cohort was grouped into pulmonary mucoepidermoid carcinoma (PMEC) and lung adenocarcinoma (LUAD) with an additional sample being adenosquamous carcinoma (ASC). DNA of tumor and normal tissue were isolated from FFPE and sequenced on a high-throughput sequencer. Data analysis was performed with an in-house validated data analysis pipeline. RESULTS: In the group of pediatric LUAD and ASC, ALK::EML4 fusions were confirmed in three of six tumors, prompting ALK-targeted treatment. We also found mutations frequently occurring in adult LUAD, such as TP53 (n = 3), KRAS and EGFR (each n = 1), but not other established druggable alterations. No smoking-related signatures were observed. One LUAD sample had a homologous recombination deficiency with a high amount of copy number alterations. In the PMEC group (n = 7), we found MAML2 fusions in all patients. Pathogenic germline variants and elevated polygenic risk scores for lung cancer were not detected in both groups. CONCLUSIONS: This study provides crucial insights into the genomic landscape across different types of pediatric lung cancer. We observed frequent presence of ALK fusions in pediatric LUAD + ASC, which are less common in adult LUAD. Other alterations in this subgroup showed resemblance with adult LUAD findings. In pediatric PMEC, we demonstrated the ubiquitous presence of MAML2 translocations. However, the conclusions of the study are limited due to the small sample size and potential artifacts from formalin-fixed paraffin-embedded samples. In summary, the results provide better understanding of the development of rare pediatric tumors and approaches for targeted therapies.
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