EXOme Rare Cancers in Children (EXOCARE)
- Conditions
- Development DelayCancer ChildhoodPredisposition, Genetic
- Interventions
- Other: Collection of blood sample or salivaOther: Collection of a tumor sample taken before the participation of the patient in studyOther: Collection of blood sample if tumor sample is not available
- Registration Number
- NCT03472807
- Lead Sponsor
- University Hospital, Angers
- Brief Summary
Other than high-dose radiation and previous chemotherapy, few strong risk factors have been identified as causes of childhood cancer. Geneticists estimate that 5 to 10% of all cancers diagnosed during the paediatric period occur in children born with a genetic mutation, increasing their lifetime risk of neoplasia. Such genetic risk is higher in children with congenital anomalies and specific genetic syndromes. Some germline genetic alterations are well known (e.g. P53 protein (P53), Neurofibromatosis type 1(NF1)), however many children with none of these mutations have clinical presentations that strongly suggest the involvement of a genetic predisposition. Comprehensive genetic testing for all such patients is an important factor for improving disease surveillance. Such opportunities are now available thanks to whole exome sequencing (WES). In oncology, an important clinical application of WES will be to routinely identify mutations associated with inherited cancer predispositions and to guide cancer risk-management decisions.
Our project is a national translational multicenter genetics study aimed at identifying genes involved in paediatric cancer predisposition by WES in a very select population of children with both developmental delay and cancer. Our project relies on the TED register (Tumeur Et Développement), an initiative by the French organisation SFCE (Société Française de lutte contre les Cancers et les leucémies de l'Enfant et de l'Adolescent) involving 30 child cancer units in France. This database includes the information of more than 500 paediatric cancer patients with congenital abnormalities. The investigators plan to sequence the germline and tumour exome of 100 patients with developmental delay in a trio-design consisting of 300 people and 100 tumours.
The investigators believe that the ExoCaRe project will provide answers to the genetic origins of certain particular childhood cancers. The ExoCaRe project relies on a genetic study to identify genetic risk factors for rare forms of childhood cancer and aims to establish more personalised treatment. It is aimed at improving genetic counselling for families and will be fully integrated in the genetic counselling process. The information provided by our study will be used to improve the management approach to an initial cancer by clarifying the risks of other cancers in related families. The investigators hope to identify new germline genes predisposing to cancer that will be of interest in understanding tumour biology.
- Detailed Description
-Primary objective : Our aim is to identify new mutations and genes involved in paediatric cancer predisposition associating developmental delay by WES of a sub-cohort of patients included in the TED database.
-Secondary objectives :
1. Describe inherited predisposition to cancer.
2. Improve genetic counselling processes.
3. Initiate clinical exome sequencing in childhood cancer treatment.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 169
-
For "Patient cancer" :
- Child having developed a cancer combined with a delay of development and\or an intellectual deficiency before the age of 18 years and followed for a cancer of the child in one of hospital center of the Société Française de lutte contre les Cancers et les leucémies de l'Enfant et de l'adolescent (SFCE)
- At least a parent still alive and available to make genetic analyses
-
For "Parent of cancer patient" :
- Parent whose child meets the criteria of inclusion of "Cancer patient"
-
For "Cancer patient" :
- Genetic predisposition already identified at the child
- Absence of histological confirmation
- Child died without DNA of the available germinal lineage
-
For "Parent of cancer patient" :
- Parent whose child doesn't meets the criteria of inclusion of "Cancer patient"
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Cancer patient Collection of blood sample if tumor sample is not available * Collection of blood sample or saliva * Collection of a tumor sample taken before the participation of the patient in study * Collection of blood sample if tumor sample is not available Parent of cancer patient Collection of blood sample or saliva -Collection of blood sample or saliva Cancer patient Collection of blood sample or saliva * Collection of blood sample or saliva * Collection of a tumor sample taken before the participation of the patient in study * Collection of blood sample if tumor sample is not available Cancer patient Collection of a tumor sample taken before the participation of the patient in study * Collection of blood sample or saliva * Collection of a tumor sample taken before the participation of the patient in study * Collection of blood sample if tumor sample is not available
- Primary Outcome Measures
Name Time Method Number and type of germline and somatic genetic variants of pathological significance and associated with the disease. At inclusion WES and RNA sequence data will be used to identify and characterise germline and somatic genetic variants of pathological significance and associated with the disease.
Descriptive statistics, such as counts and proportions of variants of pathological significance risk will be computed within each patient and family.
- Secondary Outcome Measures
Name Time Method Related to secondary objectives (3) : Number of clinical criteria justifying a WES. At inclusion Descriptive statistics, such as counts and proportions of success by clinical presentation of the disease, by cancer types, by features of developmental delay, and, by class of age.
Related to secondary objectives (1) : Identification of biological pathways involved in childhood cancer predisposition. At inclusion The deleterious mutations that the investigators will identify in genes related to childhood cancer predisposition will help to have a comprehensive framework of biological pathways involved in childhood cancer predisposition.
Related to secondary objectives (2) : Overall success rate. At inclusion Success is defined by the combined successes of quality interpretable genomic data are generated from sequencing tumor and germline tissues, and communicating genomic test results to the primary oncologist and the patient and his/her parents.
Trial Locations
- Locations (27)
University Hospital of Amiens
🇫🇷Amiens, France
University Hospital of Angers
🇫🇷Angers, France
Cancer Center Bergonie Institut
🇫🇷Bordeaux, France
University Hospital of Bordeaux
🇫🇷Bordeaux, France
University Hospital of Brest
🇫🇷Brest, France
University Hospital of Clermont Ferrand
🇫🇷Clermont-Ferrand, France
University Hospital of Dijon
🇫🇷Dijon, France
University Hospital of Grenoble
🇫🇷Grenoble, France
University Hospital of Lille
🇫🇷Lille, France
University Hospital of Limoges
🇫🇷Limoges, France
Institut of Haematology and Paediatric Oncology of Lyon
🇫🇷Lyon, France
University Hospital of Marseille
🇫🇷Marseille, France
University Hospital of Montpellier
🇫🇷Montpellier, France
University Hospital of Nancy
🇫🇷Nancy, France
University Hospital of Nantes
🇫🇷Nantes, France
University Hospital of Nice
🇫🇷Nice, France
Institut Curie
🇫🇷Paris, France
University Hospital of Kremlin Bicetre
🇫🇷Paris, France
University Hospital of Necker
🇫🇷Paris, France
University Hospital of Trousseau
🇫🇷Paris, France
University Hospital of Rennes
🇫🇷Rennes, France
University Hospital of Rouen
🇫🇷Rouen, France
University Hospital of Saint Etienne
🇫🇷Saint-Étienne, France
University Hospital of Strasbourg
🇫🇷Strasbourg, France
University Hospital of Tours
🇫🇷Tours, France
Institut Gustave Roussy
🇫🇷Villejuif, France
University Hospital of Saint Denis de La Reunion
🇷🇪Saint-Denis, Réunion