Exome analysis of tumor DNA and constitutional DNA in patients included in 1st line treatment

Exome analysis

François Ghiringhelli, PU-PH

Emilie Rederstorff, PhD

Bruno CHAUFFERT, MD

Laura MANSI, MD

Antoine ITALIANO, MD

Antoine DROUILLARD, MD

Benoist CHIBAUDEL, MD

Nicolas PENEL, MD

Jaafar BENNOUNA, MD

Nicolas Isanbert, MD

Charles Coutant, PU-PH

The "simple" analysis of the exome can determine somatic and constitutional mutations. The major challenge lies in the translation of sequencing data into clinically relevant information allowing the clinician to guide his decision-making A "complex" analysis of the exome would provide access to structural DNA data, concerning mutational signatures, tumor mutational load, analysis of large deletions, loss of heterozygosity as well as amplification of certain genes which may have an impact on the management of patients.

No data available to date makes it possible to assess the clinical interest of the availability of its additional information resulting from a "complex" analysis compared to a "simple" analysis. The objective of the EXOMA2 study is to assess the proportion of patients for whom the proposed therapy is derived from its additional information (complex analysis) and would not have been possible with a classic exome analysis (simple analysis) .

We hereby formulate the hypothesis that a "complex" analysis on a population presenting a metastatic or locally advanced disease treated early (from the 1st line of treatment) will make it possible to determine therapeutic indications which could not be discovered with a "simple" analysis.

Exome Analysis (Complexe vs Simple) to Help the Therapeutic Decision for the Precision Medicine

A Multicenter, Prospective, Multi-organ Study to Evaluate the Clinical Benefit of an Exome "Complex" Analysis Versus an Exome "Simple" Analysis to Help the Therapeutic Decision for the Precision Medicine

Centre Georges Francois Leclerc

Symptoms and General Pathology

All Conditions

Genetic Predisposition to Disease

Disease Susceptibility

Disease Attributes

one genetic consultation and one blood test

blood sample

Laurence FAIVRE, PH

Emilie REDERSTORFF

Marie-Agnès COLLONGE-RAME

Emilie REDERSTORFF, PhD

François GHIRINGHELLI, PU PH

Laurence FAIVRE

Monique MOZELLE

Frederique CARRE-PIGEON

5 to 10% of cancers are due to the presence of a constitutional genetic alteration. It can be inherited from parents (family form) or by accident, in the first moments of life after fertilization (sporadic form). In both cases, this genetic alteration is constitutional and transmissible to descendants. It is hereditary. When an hereditary early form is suspected, several well-known genes generally involved in genetic predispositions to cancer are found by a technique called " gene panel ". However, this analysis does not always identify the genetic predisposing factors for cancer. New techniques called "high-throughput exome sequencing (SHD-E)", allow more than the analysis of the the gene panel. These analysis allow to identify alterations in other genes that could contribute to the development of cancer. The objective of the Ex²trican study is to show, from patients with early cancer (sporadic or familial form), that this approach to exome sequencing can be effective to identify new genetic risk of cancer, when the first panel analysis of genes is negative.

The main objective of this study is to evaluate the interest of the SHD-E approaches after a negative result of the analysis called " gene panel " tested in routine in order to identify a genetic factor of predisposition to the cancer.

EXOME Analysis Position in the Strategy of Genetic Predisposition Factors Identification in Early-onset Cancer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Exome Analysis (Complexe vs Simple) to Help the Therapeutic Decision for the Precision Medicine	NCT04614480	Cancer	Exome analysis	18 Years -	Centre Georges Francois Leclerc
Exome Analysis (Complexe vs Simple) to Help the Therapeutic Decision for the Precision Medicine	NCT04614480	Cancer	Exome analysis	18 Years -	Centre Georges Francois Leclerc
Exome Analysis (Complexe vs Simple) to Help the Therapeutic Decision for the Precision Medicine	NCT04614480	Cancer	Exome analysis	18 Years -	Centre Georges Francois Leclerc
EXOME Analysis Position in the Strategy of Genetic Predisposition Factors Identification in Early-onset Cancer	NCT04141462	Cancer Genetic Predisp...	blood sample	18 Years -	Centre Georges Francois Leclerc

Spots Global Cancer Trial Database for exome analysis