An Investigation of Susceptibility Genes for Rare Cancers in Children by Exome Sequencing
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 169
- 试验地点
- 29
- 主要终点
- Number and type of germline and somatic genetic variants of pathological significance and associated with the disease.
研究概览
简要总结
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.
详细描述
-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 :
- Describe inherited predisposition to cancer.
- Improve genetic counselling processes.
- Initiate clinical exome sequencing in childhood cancer treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Factorial
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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"
排除标准
- •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"
结局指标
主要结局
Number and type of germline and somatic genetic variants of pathological significance and associated with the disease.
时间窗: 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.
次要结局
- Related to secondary objectives (3) : Number of clinical criteria justifying a WES.(At inclusion)
- Related to secondary objectives (1) : Identification of biological pathways involved in childhood cancer predisposition.(At inclusion)
- Related to secondary objectives (2) : Overall success rate.(At inclusion)