EXOme Rare Cancers in Children (EXOCARE)
EXOme Rare Cancers in Children (EXOCARE)
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.
-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.
Inclusion Criteria:

 -  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"

 Exclusion Criteria:

 -  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"