Optimization of the diagnosis of inherited colorectal cancer using NGS and capture of exonic and intronic sequences of panel genes

Stéphanie Baert-Desurmont; Sophie Coutant; Françoise Charbonnier; Pierre Macquere; François Lecoquierre; Mathias Schwartz; Maud Blanluet; Myriam Vezain; Raphaël Lanos; Olivier Quenez; Jacqueline Bou; Emilie Bouvignies; Steeve Fourneaux; Sandrine Manase; Stéphanie Vasseur; Jacques Mauillon; Marion Gerard; Régine Marlin; Gaëlle Bougeard; Julie Tinat; Thierry Frebourg; Isabelle Tournier

doi:10.1038/s41431-018-0207-2

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Optimization of the diagnosis of inherited colorectal cancer using NGS and capture of exonic and intronic sequences of panel genes

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Optimization of the diagnosis of inherited colorectal cancer using NGS and capture of exonic and intronic sequences of panel genes

Stéphanie Baert-Desurmont, Sophie Coutant, Françoise Charbonnier, Pierre Macquere, François Lecoquierre, Mathias Schwartz, Maud Blanluet, Myriam Vezain, Raphaël Lanos, Olivier Quenez, …

European journal of human genetics : EJHG, Vol.26(11), pp.1597-1602

01/11/2018

DOI: https://doi.org/10.1038/s41431-018-0207-2

PMID: 29967336

Résumé

Adult

Colorectal Neoplasms - diagnosis

Colorectal Neoplasms - genetics

Exons

Female

Genetic Testing - methods

Genetic Testing - standards

High-Throughput Nucleotide Sequencing - methods

High-Throughput Nucleotide Sequencing - standards

Humans

Introns

Male

Middle Aged

Reproducibility of Results

Sensitivity and Specificity

Sequence Analysis, DNA - methods

Sequence Analysis, DNA - standards

We have developed and validated for the diagnosis of inherited colorectal cancer (CRC) a massive parallel sequencing strategy based on: (i) fast capture of exonic and intronic sequences from ten genes involved in Mendelian forms of CRC (MLH1, MSH2, MSH6, PMS2, APC, MUTYH, STK11, SMAD4, BMPR1A and PTEN); (ii) sequencing on MiSeq and NextSeq 500 Illumina platforms; (iii) a bioinformatic pipeline that includes BWA-Picard-GATK (Broad Institute) and CASAVA (Illumina) in parallel for mapping and variant calling, Alamut Batch (Interactive BioSoftware) for annotation, CANOES for CNV detection and finally, chimeric reads analysis for the detection of other types of structural variants (SVs). Analysis of 1644 new index cases allowed the identification of 323 patients with class 4 or 5 variants, corresponding to a 20% disease-causing variant detection rate. This rate reached 37% in patients with Lynch syndrome, suspected on the basis of tumour analyses. Thanks to this strategy, we detected overlapping phenotypes (e.g., MUTYH biallelic mutations mimicking Lynch syndrome), mosaic alterations and complex SVs such as a genomic deletion involving the last BMPR1A exons and PTEN, an Alu insertion within MSH2 exon 8 and a mosaic deletion of STK11 exons 3-10. This strategy allows, in a single step, detection of all types of CRC gene alterations including SVs and provides a high disease-causing variant detection rate, thus optimizing the diagnosis of inherited CRC.

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Titre: Optimization of the diagnosis of inherited colorectal cancer using NGS and capture of exonic and intronic sequences of panel genes
Créateurs - sans rôle: Stéphanie Baert-Desurmont - Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
Sophie Coutant - Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
Françoise Charbonnier - Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
Pierre Macquere - Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
François Lecoquierre - Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
Mathias Schwartz - Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
Maud Blanluet - Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
Myriam Vezain - Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
Raphaël Lanos - Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
Olivier Quenez - Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
Jacqueline Bou - Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
Emilie Bouvignies - Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
Steeve Fourneaux - Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
Sandrine Manase - Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
Stéphanie Vasseur - Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
Jacques Mauillon - Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
Marion Gerard - Department of Genetics, F14000 and Normandie Univ, Normandy Centre for Genomic and Personalized Medicine, Caen University Hospital, Caen, France
Régine Marlin - Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
Gaëlle Bougeard - Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
Julie Tinat - Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
Thierry Frebourg - Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France. Frebourg@chu-rouen.fr
Isabelle Tournier - Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
Détails de publication: European journal of human genetics : EJHG, Vol.26(11), pp.1597-1602
Identifiants: 99163233309311
Unité académique: Institut des Biomolécules Max Mousseron - IBMM
Langue: English
Type de ressource: Journal article