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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Colorectal Cancer; Ovarian Cancer; Pediatric Cancers; Multiple Primary Malignant Tumours
• Intervention / Treatment: Genetic: Genetic analysis

• Study Type: Interventional
• Enrollment (Actual): 289
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Rouen, France, 76031
    • ROUEN university hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Genetic analysis of patient with early-onset breast cancer; Sequencing of 200 selected genes in patient with early-onset breast cancer without genomic alterations of BRCA1, BRCA2 or TP53	Genetic: Genetic analysis; Sequencing of 200 selected genes in the different study populations
Experimental: Genetic analysis of patient with early-onset ovarian cancer; Sequencing of 200 selected genes in patient with early-onset ovarian cancer without genomic alterations of BRCA1, BRCA2	Genetic: Genetic analysis; Sequencing of 200 selected genes in the different study populations
Experimental: Genetic analysis of patient with pediatric cancer; Sequencing of 200 selected genes in patient with pediatric cancer without genomic alteration of TP53	Genetic: Genetic analysis; Sequencing of 200 selected genes in the different study populations
Experimental: Genetic analysis of patient with early-onset colorectal cancer; 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; Sequencing of 200 selected genes in the different study populations
Experimental: Genetic analysis of patient with multiple primary tumors; Sequencing of 200 selected genes in patient with Multiple primary malignant tumors without syndromic presentation	Genetic: Genetic analysis; Sequencing of 200 selected genes in the different study populations

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Rouen
• Investigators: Principal Investigator: Thierry FREBOURG, Pr, ROUEN university hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): March 15, 2017
• Study Completion (Actual): March 15, 2017

Study Registration Dates

• First Submitted: January 22, 2016
• First Submitted That Met QC Criteria: January 22, 2016
• First Posted (Estimate): January 27, 2016

Study Record Updates

• Last Update Posted (Actual): June 30, 2020
• Last Update Submitted That Met QC Criteria: June 26, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: 2015/160/HP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO