Finding New Targets by Proteomic Approaches (InnovRT1) (InnovRT1)

Heterogeneity in Rhabdoid Tumors : Proteomic and Single-Cell Analyses to Identify New Therapeutic Targets

The investigators aim to explore the inter tumor heterogeneity by a proteomic approach of a wide series of rhabdoid tumors, from both intra and extra cranial origins.

Study Overview

• Status: Completed
• Conditions: ATRT
• Intervention / Treatment: Biological: Mass spectrometry

Detailed Description

Context: Rhaboid tumors (RT) are aggressive cancers of young infants, exposed to the toxicity of heavy treatments often ineffective, which justifies the need to identify new treatment strategies. These tumors are characterized by the biallelic alteration of SMARCB1 gene, encoding one of the subunits of the SWI/SNF complex, a chromatin remodeler. These mutations are the only ones found in these very stable cancers, which offers few therapeutic targets that can be identified by genomic techniques. They are morphologically undifferentiated and pluriphenotypic, suggesting the existence of a cellular diversity still poorly described. To advance on these questions, the investigators' laboratory has developed a model of genetically engineered mouse model spontaneously developing RT, biologically very similar to their human counterparts.

Objectives and methods: The investigators' project aims to describe the proteomic and phosphoproteomic signatures of these tumors, so far described at the genome and transcriptome level; an integration of these pangenomic / pan-proteomic studies will reveal the most relevant features to target. The investigators will fully characterize the proteomic and phosphoproteomic landscape using mass spectrometry on a cohort of clinically, radiologically and histopathologically annoted ATRT, for which methylome and RNAseq profiling will also be done. The investigators will describe the proteomic features of each molecularly defined subgroups, and aim to correlate RNAseq changes with proteomic features.

Patients will be included if they or their legal representative have given a consent to such a study, and if frozen material is stored at Necker Hospital.

Expected results: This analysis helps to identify how to articulate several innovative therapeutic approaches, taking into account both the diversity of the cells to be treated, and the real targets, proteins, to inhibit or restore.

• Study Type: Observational
• Enrollment (Actual): 44

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Service de neurochirurgie - Hôpital Necker Enfants malades

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

cohort of clinically, radiologically and histopathologically annoted ATRT

Description

Inclusion Criteria:

• Aged 0-17 years old
• Rhabdoid tumor, treated in oncology departments in Ile de France
• frozen samples collected in usual care
• parents' agreement for samples collection in usual care

Exclusion Criteria

• Unconfirmed diagnosis of Rhabdoid tumor with molecular analyses Samples
• paraffin embedded tissues

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ATRT; Patients <18 years with an ATRT having frozen samples	Biological: Mass spectrometry; Characterization of the proteomic and phosphoproteomic landscape using mass spectrometry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Identification of proteomic signature for each molecular subgroup of ATRT	3 years

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Institut Curie; URC-CIC Paris Descartes Necker Cochin; Sainte Anne hospital
• Investigators: Study Director: Kevin Beccaria, MD, PhD, APHP Assistance Publique des Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2022
• Primary Completion (Actual): February 17, 2023
• Study Completion (Actual): February 17, 2023

Study Registration Dates

• First Submitted: April 29, 2021
• First Submitted That Met QC Criteria: April 29, 2021
• First Posted (Actual): May 3, 2021

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: ATRT; Brain Tumors; Multi-omics; SMARCB1; Proteomic
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Neoplasms; Investigative Techniques; Chemistry Techniques, Analytical; Mass Spectrometry
• Other Study ID Numbers: APHP201123

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No