Targeted Next-generation Sequencing Panel for Identification of Germline Mutations in Early Onset Cancers With Sporadic or Hereditary Presentation

Study Overview
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Brief Summary
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Despite relevant clinical and/or familial presentations suggesting a hereditary predisposition (early-onset, multiple primary tumors, familial aggregation), targeted genomic analysis based on the phenotype are often non contributive. As somatic cancer genes are limited, the hypothesis is that the targeted next-generation sequencing of 200 genes, selected for their implications in cancers may contribute to the understanding of many selected patients' presentation by the identification of germline deleterious mutations, and may identified phenotype overlapping and/or mosaicisms. The focus will be put on early-onset breast, ovarian, colorectal cancer or pediatric cancers and multiple primary tumors.

Official Title
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Targeted Next-generation Sequencing Panel for Identification of Germline Mutations in Early Onset Cancers With Sporadic or Hereditary Presentation

Conditions
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Breast Cancer, Ovarian Cancer, Colorectal Cancer, Pediatric Cancers, Multiple Primary Malignant Tumours

Intervention / Treatment
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* Genetic: Genetic analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria : Older than 18 or parental agreement in case of children. For patient with early-onset breast cancer : Invasive breast cancer, regardless of histological type or stage, diagnosed before 31 years. Sporadic or familial presentation No genomic alterations of BRCA1, BRCA2 or TP53 For patient with early-onset ovarian cancer : Invasive ovarian cancer, regardless of histological type or stage, diagnosed before 41 years. Sporadic or familial presentation No genomic alterations of BRCA1, BRCA2 Patient with early-onset colorectal cancer : Invasive colorectal cancer diagnosed before 31 years. Sporadic or familial presentation No genomic alteration of MSH2, MLH1 or MSH6 in case of HNPCC presentation No genomic alteration of APC, MUTYH, SMAD4, BMPR1A, PTEN or STK11 in case of adenomatous polyposis or hamartoma presentation Patient with pediatric cancer : Non haematological tumour diagnosed before 16 years, with Li-Fraumeni presentation. No genomic alteration of TP53 Patient with Multiple primary malignant tumours : Multiple synchronous or metachronous primary malignant tumors with early-onset No syndromic presentation Exclusion Criteria: Any already known deleterious mutations according to the patient's phenotype
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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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Genetic analysis of patient with early-onset breast cancer<br>Sequencing of 200 selected genes in patient with early-onset breast cancer without genomic alterations of BRCA1, BRCA2 or TP53 | Genetic: Genetic analysis<br>* Sequencing of 200 selected genes in the different study populations<br>|
| Experimental: Genetic analysis of patient with early-onset ovarian cancer<br>Sequencing of 200 selected genes in patient with early-onset ovarian cancer without genomic alterations of BRCA1, BRCA2 | Genetic: Genetic analysis<br>* Sequencing of 200 selected genes in the different study populations<br>|
| Experimental: Genetic analysis of patient with pediatric cancer<br>Sequencing of 200 selected genes in patient with pediatric cancer without genomic alteration of TP53 | Genetic: Genetic analysis<br>* Sequencing of 200 selected genes in the different study populations<br>|
| Experimental: Genetic analysis of patient with early-onset colorectal cancer<br>Sequencing of 200 selected genes in patient with early-onset colorectal cancer without genomic alteration of APC, MUTYH, SMAD4, BMPR1A, PTEN or STK11 in case of adenomatous polyposis or hamartoma presentation or without genomic alteration of MSH2, MLH1 or MSH6 in case of HNPCC presentation | Genetic: Genetic analysis<br>* Sequencing of 200 selected genes in the different study populations<br>|
| Experimental: Genetic analysis of patient with multiple primary tumors<br>Sequencing of 200 selected genes in patient with Multiple primary malignant tumors without syndromic presentation | Genetic: Genetic analysis<br>* Sequencing of 200 selected genes in the different study populations<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of germline deleterious mutations | Frequency of germline deleterious mutations will be assessed for the 200 selected genes using next generation sequencing method | Day 1 |