Molecular Basis of Pediatric Liver Cancer

Study Overview
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Brief Summary
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The purpose of this retrospective and prospective project is to understand the molecular and genetic basis of liver cancer of childhood. Understanding the molecular and genetic bases of liver cancers can offer a better classification based on tumor biology, mechanisms and predisposition.

Detailed Description
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Pediatric liver cancers are rare, affecting at times no more than 1 in one million population. Understanding the molecular basis of these cancers is important in order to develop more accurate diagnoses and more effective treatments. Current classifications of these cancers are based on how these cancers look on diagnostic studies such as radiologic imaging or under the microscope. Such a classification system does not explain why a particular cancer has a different outcome from what is considered usual for that particular cancer. Nor does such a classification system explain why two different classes of cancers behave the same way. Understanding the genetic bases of liver cancers can offer a better classification based on tumor biology, mechanisms and predisposition. To achieve these goals, large numbers of such cancer patients or affected tissue must be collected. This is not possible in any single institution, or any single country. The current project will collect biological samples such as residual tumor tissue, saliva, or blood from affected patients and their biological parents and families, along with clinical information about the cancer. These biological samples will be used to study the genes and how these genes work in tumor tissue and in non-tumor tissue. The results of this study will permit childhood liver cancers to be categorized on the basis of common defects in genes and their function.

Official Title
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Genetic and Molecular Basis of Pediatric Liver Cancer

Conditions
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Childhood Liver Cancer, Liver Malignant Tumors, Embryonal Sarcoma of Liver (Disorder), Hepatoblastoma, Hepatocellular Carcinoma, Rhabdoid Tumor of Liver

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prior or current treatment for a childhood liver tumor, malignant or benign, at age <21 years. Biological parents and siblings of eligible children. Exclusion Criteria: No prior or current treatment for a childhood liver tumor. Non-biological parents, legal guardians, or non-biological siblings of eligible children.

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gene sequencing | DNA sequence variants | Recurrence free survival at 2 years | 
| Gene expression analysis | Differentially expressed genes | Recurrence free survival at 2 years | 
| Status of genome-wide chromatin accessibility | chromatin accessibility | Duration of active chemotherapy to two years after surgical treatment | 
| Epigenetic change | Differential methylation | Duration of active chemotherapy to two years after surgical treatment | 
| Tumor infiltrating cells which express immune checkpoints | differentially enriched immune cells | Duration of active chemotherapy to two years after surgical treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to chemotherapy | Survival | Duration of active chemotherapy to two years after surgical treatment | 
| Response to chemotherapy | Relapse | Duration of active chemotherapy to two years after surgical treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatoblastoma, Hepatocellular Carcinoma, Pediatric Liver Cancer