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

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

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.

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