Whole Exome and Genome analysis to define Childhood Cancer Germline Genomic Landscape, identify new cancer predisposition genes, and develop, validate India-specific multigene panels for inherited paediatric cancers.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 1,815
- 试验地点
- 8
- 主要终点
- To study the prevalence and spectrum of pathogenic germline mutations in cancer predisposition genes in 3 distinct groups of childhood cancer (CNS, Haematolymphoid, and Pediatric solid tumours) not selected for family history or syndromic features.
研究概览
简要总结
This study aims to investigate genetic risk factors in childhood cancers by analyzing the DNA of 2,500 pediatric cancer patients from nine major oncology centers across India. Whole Exome Sequencing (WES) will be performed on all cases, which is a technique that examines only the protein-coding regions of genes (about 1-2% of the entire genome) where most disease-causing mutations are found. This is done by extracting DNA from a blood sample, preparing it in a lab to isolate these specific regions, and then using advanced machines to "read" the genetic code. In 300 selected cases, a more detailed analysis called Whole Genome Sequencing (WGS) will be conducted, which examines the entire genetic material of a person, including both protein-coding and non-coding regions. WGS helps identify mutations that might be missed by WES, such as structural changes in DNA. The genetic variations found will be classified according to internationally recognized guidelines to determine whether they are harmful or harmless. If a harmful mutation is identified, family members will also be tested to check if they carry the same inherited genetic change. Based on these findings, the study will develop and validate cost-effective, targeted multigene panels, which are smaller, customized genetic tests that focus only on the key cancer-related genes, making them more affordable and practical for routine use in India. Families of affected children will receive genetic counseling, where experts will explain the test results, discuss potential cancer risks, and guide them on further monitoring or preventive measures. To ensure that more families benefit from these findings, strategies will be tested to improve participation in genetic screening and high-risk cancer monitoring programs. If certain mutations are found to be more common in specific ethnic groups, the study will also explore whether newborn screening for these mutations is feasible to help detect risks early in life. The results of this study will help personalize cancer treatment for children, contribute to national guidelines for genetic testing, and improve long-term care strategies for affected families. Throughout the study, strict ethical guidelines and confidentiality measures will be followed to protect patient data and privacy.
研究设计
- 研究类型
- Observational
入排标准
- 年龄范围
- 1.00 Year(s) 至 18.00 Year(s)（—）
- 性别
- All
入选标准
- •Age at first cancer diagnosis less than equal to 18 years
- •Histopathologically confirmed cancer diagnosis
- •Patients in whom tumour biopsy is not possible or mandatory due to location or nature of tumour (such as brain stem or optic pathway glioma, intraocular tumours or specific liver or germ cell tumors) should have an unequivocal diagnosis of a specific cancer based on pathognomonic Clinico Radiological features including or excluding elevated tumor markers.
- •Diagnosed with primary, second primary or relapsed cancer in the previous 6 months, with exceptions made to include rare cancers like choroid plexus carcinoma, adrenocortical carcinoma at any time from diagnosis.
- •Parents or patients (more than 18 years) informed consent for the study.
排除标准
- •Incomplete or inconclusive histological, cytogenetic or molecular examination needed to establish an unequivocal diagnosis of cancer and its subtype.
结局指标
主要结局
To study the prevalence and spectrum of pathogenic germline mutations in cancer predisposition genes in 3 distinct groups of childhood cancer (CNS, Haematolymphoid, and Pediatric solid tumours) not selected for family history or syndromic features.
时间窗: Post-enrollment, typically after the sample is processed and results reported. Sampling is expected within the study duration after whole exome sequencing/whole genome sequencing. Survival will be calculated at the end of study period from the time of primary malignancy diagnosis (for relapse patients in the study, from the date of diagnosis of first malignancy) to the occurrence of relapse, progression, death, or the occurrence of second malignant neoplasm or last follow up if no events occur
次要结局
- 1. Based on the frequency of germline mutation in different CPS genes, develop and validate new targeted multigene panels(2. Identify and validate new CPS Genes)
研究者
Dr Rajiv Sarin
Tata Memorial Hospital and ACTREC