Abstract 1204: Very high throughput genome sequencing for pediatric cancers in France

Abstract Background: The France Genomic Medicine Plan (PFMG) 2025 has established very high throughput genome sequencing (HTS; including paired germline/tumor WGS 60x, WES 150x, and RNAseq) in clinical care for patients with cancer within the framework of 12 indications since March 2020. Results: Two of the predefined indications apply to pediatric malignancies and led to 1475 prescriptions until October 2024, i.e. 48% of those in all cancer patients. Prescription in the context of “treatment failure” (all tumor types) represents 64% of prescriptions. Initially established within the MOSCATO-01 and MAPPYACTS studies, a multidisciplinary national clinical molecular tumor board (CMTB) evaluates the conclusions of all HTS reports to propose personalized therapeutic interventions to clinical prescribers including information on available clinical trials. HTS identified at least one somatic molecular alteration considered potentially relevant for 90% of prescriptions at “treatment failure” (487/546). At least one adapted targeted therapy was recommended for 77% of the discussed cases (366/471). Recently, the multicenter study MAPPYACTS 2 (NCT05691608) accompanies PFMG to analyze the survival benefit of novel therapies identified by the CMTB. This study also allows the implementation of ancillary projects such as circulating biomarkers. For 5 pediatric cancers types for which HTS has been validated at diagnosis (leukemia, neuroblastoma, brain tumor, rare tumors, osteosarcomas), the contribution of HTS compared to tumor molecular analyses carried out within routine care is currently being evaluated via the PFMG vs Standard of Care CARE-Seq study. In the field of oncogenetics, analyses of “incidental” constitutional data from the HTS provides important insights allowing the discovery of a predisposition gene for cancers. Other more fundamental studies will include an analysis of VUS-type variations with integration of AI (same as the PCM4U adult project with classifier) ​​in pediatric tumors or exploration of molecular mechanisms of oncogenesis, or treatment resistance including the study of non-coding RNAs, the study of the structure around telomeres, centromeres, or tumor type-specific alterations. The clinical ‘pre-indications’ are subjected to a medico-economic analysis to determine which will eventually be covered by the French Health Insurance System and become ‘clinical indications’. Conclusion: The integrative molecular approach including HTS in standard of care constitutes a crucial tool for developing national or international collaborative research studies aimed at improving the care of children and adolescents with cancer. Citation Format: Ludovic Lacroix, Gaelle Pierron, Julien Masliah Planchon, Marc Barritault, Adrien Buisson, Alain Viari, Tiphaine Adam-De-Beaumais, Gaelle Tachon, Valery Attignon, Helene Cavé, Helene Lapillonne, Pascale Flandrin-Gresta, Eric Delabesse, Sylvie Tondeur, Mathilde Laubert, Isabelle Rochet, Imene Hezam, Silvana Beatriz Dangiolo, Samuel Abbou, Pablo Berlanga, Jacques Grill, Franck Bourdeaut, Natacha Entz-Werle, Pierre Leblond, Nicolas André, Gabriel Revon-Riviere, Antony Ceraulo, Marion Strullu, Pierre Rohrlich, Arnaud Petit, Stephane Ducassou, Lea Guerrini-Rousseau, Claudia Pasqualini, Gudrun Schleiermacher, Nadege Corradini, Birgit Geoerger. Very high throughput genome sequencing for pediatric cancers in France [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1204.