Research Papers:

Non-invasive detection of somatic mutations using next-generation sequencing in primary central nervous system lymphoma

Maxime Fontanilles, Florent Marguet, Élodie Bohers, Pierre-Julien Viailly, Sydney Dubois, Philippe Bertrand, Vincent Camus, Sylvain Mareschal, Philippe Ruminy, Catherine Maingonnat, Stéphane Lepretre, Elena-Liana Veresezan, Stéphane Derrey, Hervé Tilly, Jean-Michel Picquenot, Annie Laquerrière and Fabrice Jardin _

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Oncotarget. 2017; 8:48157-48168. https://doi.org/10.18632/oncotarget.18325

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Maxime Fontanilles1,2, Florent Marguet3,4, Élodie Bohers2, Pierre-Julien Viailly2, Sydney Dubois2, Philippe Bertrand2, Vincent Camus1,2, Sylvain Mareschal2, Philippe Ruminy2, Catherine Maingonnat2, Stéphane Lepretre1, Elena-Liana Veresezan5, Stéphane Derrey6, Hervé Tilly1,2, Jean-Michel Picquenot5, Annie Laquerrière3,4 and Fabrice Jardin1,2

1Department of Hematology, Cancer Center Henri Becquerel, 76000 Rouen, France

2INSERM U1245, Cancer Center Henri Becquerel, Institute of Research and Innovation in Biomedicine (IRIB), University of Normandy, UNIVROUEN, 76000 Rouen, France

3INSERM U1245 and Hôpital Charles Nicolle, NeoVasc Team, University of Normandy, UNIVROUEN, CHU-Hôpitaux de Rouen, 76031 Rouen, France

4Department of Neuropathology, Hôpital Charles Nicolle, Normandy Center for Genomic and Personalized Medicine, CHU-Hôpitaux de Rouen, 76031 Rouen, France

5Department of Pathology, Cancer Center Henri Becquerel, 76000 Rouen, France

6Department of Neurosurgery, Hôpital Charles Nicolle, CHU-Hôpitaux de Rouen, 76031 Rouen, France

Correspondence to:

Fabrice Jardin, email: fabrice.jardin@chb.unicancer.fr

Keywords: primary central nervous system lymphoma, circulating cell-free tumor DNA, somatic mutation, liquid biopsy, next-generation sequencing

Received: March 08, 2017    Accepted: May 03, 2017    Published: June 01, 2017


Purpose: Primary central nervous system lymphomas (PCNSL) have recurrent genomic alterations. The main objective of our study was to demonstrate that targeted sequencing of circulating cell-free DNA (cfDNA) released by PCNSL at the time of diagnosis could identify somatic mutations by next-generation sequencing (NGS).

Patients and Methods: PlasmacfDNA and matched tumor DNA (tDNA) from 25 PCNSL patients were sequenced using an Ion Torrent Personal Genome Machine (Life Technologies®). First, patient-specific targeted sequencing of identified somatic mutations in tDNA was performed. Then, a second sequencing targeting MYD88 c.T778C was performed and compared to plasma samples from 25 age-matched control patients suffering from other types of cancer.

Results: According to the patient-specific targeted sequencing, eight patients (32% [95% CI 15-54%]) had detectable somatic mutations in cfDNA. Considering MYD88 sequencing, six patients had the specific c.T778C alteration detected in plasma. Using a control group, the sensitivity was 24% [9-45%] and the specificity was 100%. Tumor volume or deep brain structure involvement did not influence the detection of somatic mutations in plasma.

Conclusion: This pilot study provided evidence that somatic mutations can be detected by NGS in the cfDNA of a subset of patients suffering from PCNSL.

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