Pediatric Patient-Derived-Xenograft development in MAPPYACTS – international pediatric cancer precision medicine trial in relapsed and refractory tumors

Pediatric patients with recurrent and refractory cancers are in most need for new treatments. This study developed patient-derived-xenograft (PDX) models within the European MAPPYACTS cancer precision medicine trial (NCT02613962). To date, 131 PDX models were established following heterotopical and/or orthotopical implantation in immunocompromised mice: 76 sarcomas, 25 other solid tumors, 12 central nervous system tumors, 15 acute leukemias, and 3 lymphomas. PDX establishment rate was 43%. Histology, whole exome and RNA sequencing revealed a high concordance with the primary patient’s tumor profile, human leukocyte-antigen characteristics and specific metabolic pathway signatures. A detailed patient molecular characterization, including specific mutations prioritized in the clinical molecular tumor boards are provided. Ninety models were shared with the IMI2 ITCC Paediatric Preclinical Proof-of-concept Platform (IMI2 ITCC-P4) for further exploitation. This new PDX biobank of unique recurrent childhood cancers provides an essential support for basic and translational research and new treatments development in advanced pediatric malignancies.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 2 Publications

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Dataset ID	Description	Technology	Samples
EGAD00001011048	Pediatric patients with recurrent and refractory cancers are in most need for new treatments. This study developed patient-derived-xenograft (PDX) models within the European MAPPYACTS cancer precision medicine trial (NCT02613962). To date, 131 PDX models were established following heterotopical and/or orthotopical implantation in immunocompromised mice: 76 sarcomas, 25 other solid tumors, 12 central nervous system tumors, 15 acute leukemias, and 3 lymphomas. PDX establishment rate was 43%. Histology, whole exome and RNA sequencing revealed a high concordance with the primary patient’s tumor profile, human leukocyte-antigen characteristics and specific metabolic pathway signatures. A detailed patient molecular characterization, including specific mutations prioritized in the clinical molecular tumor boards are provided. Ninety models were shared with the IMI2 ITCC Paediatric Preclinical Proof-of-concept Platform (IMI2 ITCC-P4) for further exploitation. This new PDX biobank of unique recurrent childhood cancers provides an essential support for basic and translational research and new treatments development in advanced pediatric malignancies.	Illumina HiSeq 4000 Illumina NovaSeq 6000 NextSeq 500	166

Publications	Citations
A biobank of pediatric patient-derived-xenograft models in cancer precision medicine trial MAPPYACTS for relapsed and refractory tumors. Marques Da Costa ME, Zaidi S, Scoazec JY, Droit R, Lim WC, Marchais A, Salmon J, Cherkaoui S, Morscher RJ, Laurent A, Malinge S, Mercher T, Tabone-Eglinger S, Goddard I, Pflumio F, Calvo J, Redini F, Entz-Werlé N, Soriano A, Villanueva A, Cairo S, Chastagner P, Moro M, Owens C, Casanova M, Hladun-Alvaro R, Berlanga P, Daudigeos-Dubus E, Dessen P, Zitvogel L, Lacroix L, Pierron G, Delattre O, Schleiermacher G, Surdez D, Geoerger B. Commun Biol 6: 2023 949	1
Divergent HLA variations and heterogeneous expression but recurrent HLA loss-of- heterozygosity and common <i>HLA-B</i> and <i>TAP</i> transcriptional silencing across advanced pediatric solid cancers. Lim WC, Marques Da Costa ME, Godefroy K, Jacquet E, Gragert L, Rondof W, Marchais A, Nhiri N, Dalfovo D, Viard M, Labaied N, Khan AM, Dessen P, Romanel A, Pasqualini C, Schleiermacher G, Carrington M, Zitvogel L, Scoazec JY, Geoerger B, Salmon J. Front Immunol 14: 2023 1265469	0

Publications

Citations

A biobank of pediatric patient-derived-xenograft models in cancer precision medicine trial MAPPYACTS for relapsed and refractory tumors.
Marques Da Costa ME, Zaidi S, Scoazec JY, Droit R, Lim WC, Marchais A, Salmon J, Cherkaoui S, Morscher RJ, Laurent A, Malinge S, Mercher T, Tabone-Eglinger S, Goddard I, Pflumio F, Calvo J, Redini F, Entz-Werlé N, Soriano A, Villanueva A, Cairo S, Chastagner P, Moro M, Owens C, Casanova M, Hladun-Alvaro R, Berlanga P, Daudigeos-Dubus E, Dessen P, Zitvogel L, Lacroix L, Pierron G, Delattre O, Schleiermacher G, Surdez D, Geoerger B. Commun Biol 6: 2023 949

Divergent HLA variations and heterogeneous expression but recurrent HLA loss-of- heterozygosity and common <i>HLA-B</i> and <i>TAP</i> transcriptional silencing across advanced pediatric solid cancers.
Lim WC, Marques Da Costa ME, Godefroy K, Jacquet E, Gragert L, Rondof W, Marchais A, Nhiri N, Dalfovo D, Viard M, Labaied N, Khan AM, Dessen P, Romanel A, Pasqualini C, Schleiermacher G, Carrington M, Zitvogel L, Scoazec JY, Geoerger B, Salmon J. Front Immunol 14: 2023 1265469