Oncologie pédiatrique

Publications

Année de publication : 2018

Forget Antoine, Martignetti Loredana, Puget Stéphanie, Calzone Laurence, Brabetz Sebastian, Picard Daniel, Montagud Arnau, Liva Stéphane, Sta Alexandre, Dingli Florent, Arras Guillaume, Rivera Jaime, Loew Damarys, Besnard Aurore, Lacombe Joëlle, Pagès Mélanie, Varlet Pascale, Dufour Christelle, Yu Hua, L. Mercier Audrey, Indersie Emilie, Chivet Anaïs, Leboucher Sophie, Sieber Laura, Beccaria Kevin, Gombert Michael, D. Meyer Frauke, Qin Nan, Bartl Jasmin, Chavez Lukas, Okonechnikov Konstantin, Sharma Tanvi, Thatikonda Venu, Bourdeaut Franck, Pouponnot Celio, Ramaswamy Vijay, Korshunov Andrey, Borkhardt Arndt, Reifenberger Guido, Poullet Patrick, D. Taylor Michael, Kool Marcel, M. Pfister Stefan, Kawauchi Daisuke, Barillot Emmanuel, Remke Marc, Ayrault Olivier (2018 Sep 10)

Aberrant ERBB4-SRC Signaling as a Hallmark of Group 4 Medulloblastoma Revealed by Integrative Phosphoproteomic Profiling

Cancer Cell : 34 : 379-395 : DOI : 10.1016/j.ccell.2018.08.002 En savoir plus
Résumé

The current consensus recognizes four main medulloblastoma subgroups (wingless, Sonic hedgehog, group 3 and group 4). While medulloblastoma subgroups have been characterized extensively at the (epi-)genomic and transcriptomic levels, the proteome and phosphoproteome landscape remain to be comprehensively elucidated. Using quantitative (phospho)-proteomics in primary human medulloblastomas, we unravel distinct posttranscriptional regulation leading to highly divergent oncogenic signaling and kinase activity profiles in groups 3 and 4 medulloblastomas. Specifically, proteomic and phosphoproteomic analyses identify aberrant ERBB4-SRC signaling in group 4. Hence, enforced expression of an activated SRC combined with p53 inactivation induces murine tumors that resemble group 4 medulloblastoma. Therefore, our integrative proteogenomics approach unveils an oncogenic pathway and potential therapeutic vulnerability in the most common medulloblastoma subgroup.

Replier

Année de publication : 2017

A Bertrand, C Rondenet, J Masliah-Planchon, P Leblond, A de la Fourchardière, D Pissaloux, K Aït-Raïs, D Lequin, A Jouvet, P Freneaux, H Sevestre, D Ranchere-Vince, A Tauziede-Espariat, C-A Maurage, K Silva, G Pierron, O Delattre, P Varlet, D Frappaz, F Bourdeaut (2017 Jan 6)

Rhabdoid component emerging as a subclonal evolution of paediatric glioneuronal tumours.

Neuropathology and applied neurobiology : DOI : 10.1111/nan.12379 En savoir plus
Résumé

Atypical teratoid/rhabdoid tumors (AT/RT) are high-grade tumors partially composed of rhabdoid cells (1). The 1-year overall survival rate is 41% (2). Rhabdoid cells have large eccentric nuclei, a single prominent nucleolus, and abundant cytoplasm with eosinophilic inclusions. The immunohistochemical profile of these cells frequently includes loss of nuclear BAF47 expression due to loss of the SMARCB1 locus combined with a mutation of the other allele (3). This article is protected by copyright. All rights reserved.

Replier
Gudrun Schleiermacher, Olivier Delattre (2017 Jan 2)

Kids Enter the MATCH.

Journal of the National Cancer Institute : DOI : djw305 En savoir plus
Résumé

Replier

Année de publication : 2016

Thomas Pincez, Nathalie Clément, Eve Lapouble, Gaëlle Pierron, Maud Kamal, Ivan Bieche, Virginie Bernard, Paul Fréneaux, Jean Michon, Daniel Orbach, Isabelle Aerts, Hélène Pacquement, Franck Bourdeaut, Irene Jiménez, Estelle Thébaud, Caroline Oudot, Cécile Vérité, Sophie Taque, Cormac Owens, François Doz, Christophe Le Tourneau, Olivier Delattre, Gudrun Schleiermacher (2016 Nov 30)

Feasibility and clinical integration of molecular profiling for target identification in pediatric solid tumors.

Pediatric blood & cancer : DOI : 10.1002/pbc.26365 En savoir plus
Résumé

The role of tumor molecular profiling in directing targeted therapy utilization remains to be defined for pediatric tumors. We aimed to evaluate the feasibility of a sequencing and molecular biology tumor board (MBB) program, and its clinical impact on children with solid tumors.

Replier
Mathieu Chicard, Sandrine Boyault, Leo Colmet Daage, Wilfrid Richer, David Gentien, Gaelle Pierron, Eve Lapouble, Angela Bellini, Nathalie Clement, Isabelle Iacono, Stéphanie Bréjon, Marjorie Carrere, Cécile Reyes, Toby Hocking, Virginie Bernard, Michel Peuchmaur, Nadège Corradini, Cécile Faure-Conter, Carole Coze, Dominique Plantaz, Anne Sophie Defachelles, Estelle Thebaud, Marion Gambart, Frédéric Millot, Dominique Valteau-Couanet, Jean Michon, Alain Puisieux, Olivier Delattre, Valérie Combaret, Gudrun Schleiermacher (2016 Jul 22)

Genomic copy number profiling using circulating free tumor DNA highlights heterogeneity in neuroblastoma.

Clinical cancer research : an official journal of the American Association for Cancer Research : DOI : clincanres.0500.2016 En savoir plus
Résumé

The tumor genomic copy number profile is of prognostic significance in neuroblastoma (NB) patients. We have studied the genomic copy number profile of cell free DNA (cfDNA) and compared this to primary tumor aCGH at diagnosis.

Replier
Navin Pinto, Jodi R Mayfield, Gordana Raca, Mark A Applebaum, Alexandre Chlenski, Madina Sukhanova, Rochelle Bagatell, Meredith S Irwin, Anthony Little, Jawhar Rawwas, Yasmin Gosiengfiao, Olivier Delattre, Isabelle Janoueix-Lerosey, Eve Lapouble, Gudrun Schleiermacher, Susan L Cohn (2016 Feb 12)

Segmental Chromosomal Aberrations in Localized Neuroblastoma Can be Detected in Formalin-Fixed Paraffin-Embedded Tissue Samples and Are Associated With Recurrence.

Pediatric blood & cancer : 1019-23 : DOI : 10.1002/pbc.25934 En savoir plus
Résumé

Array comparative genomic hybridization (CGH) analyses of frozen tumors have shown strong associations between the pattern of chromosomal aberrations and outcome in patients with advanced-stage neuroblastoma. New platforms for analyzing chromosomal aberrations using formalin-fixed paraffin-embedded (FFPE) tissue have recently been developed. We sought to determine whether chromosomal microarray analysis (CMA) using FFPE tumors is feasible and if segmental chromosomal aberrations were prognostic of recurrence in localized neuroblastoma.

Replier
Zhi-Yan Han, Wilfrid Richer, Paul Fréneaux, Céline Chauvin, Carlo Lucchesi, Delphine Guillemot, Camille Grison, Delphine Lequin, Gaelle Pierron, Julien Masliah-Planchon, André Nicolas, Dominique Ranchère-Vince, Pascale Varlet, Stéphanie Puget, Isabelle Janoueix-Lerosey, Olivier Ayrault, Didier Surdez, Olivier Delattre, Franck Bourdeaut (2016 Jan 29)

The occurrence of intracranial rhabdoid tumours in mice depends on temporal control of Smarcb1 inactivation.

Nature communications : 10421 : DOI : 10.1038/ncomms10421 En savoir plus
Résumé

Rhabdoid tumours (RTs) are highly aggressive tumours of infancy, frequently localized in the central nervous system (CNS) where they are termed atypical teratoid/rhabdoid tumours (AT/RTs) and characterized by bi-allelic inactivation of the SMARCB1 tumour suppressor gene. In this study, by temporal control of tamoxifen injection in Smarcb1(flox/flox);Rosa26-Cre(ERT2) mice, we explore the phenotypes associated with Smarcb1 inactivation at different developmental stages. Injection before E6, at birth or at 2 months of age recapitulates previously described phenotypes including embryonic lethality, hepatic toxicity or development of T-cell lymphomas, respectively. Injection between E6 and E10 leads to high penetrance tumours, mainly intra-cranial, with short delays (median: 3 months). These tumours demonstrate anatomical, morphological and gene expression profiles consistent with those of human AT/RTs. Moreover, intra- and inter-species comparisons of tumours reveal that human and mouse RTs can be split into different entities that may underline the variety of RT cells of origin.

Replier