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

• Published in: Oncotarget Vol. 8; no. 29; pp. 48157 - 48168
• Main Authors: Fontanilles, Maxime, Marguet, Florent, Bohers, Élodie, Viailly, Pierre-Julien, Dubois, Sydney, Bertrand, Philippe, Camus, Vincent, Mareschal, Sylvain, Ruminy, Philippe, Maingonnat, Catherine, Lepretre, Stéphane, Veresezan, Elena-Liana, Derrey, Stéphane, Tilly, Hervé, Picquenot, Jean-Michel, Laquerrière, Annie, Jardin, Fabrice
• Format: Journal Article
• Language: English
• Published: United States Impact journals 18.07.2017; Impact Journals LLC
• Subjects: Aged; Aged, 80 and over; Alleles; Biopsy; Case-Control Studies; Central Nervous System Neoplasms - diagnosis; Central Nervous System Neoplasms - genetics; Central Nervous System Neoplasms - therapy; DNA Mutational Analysis - methods; DNA, Circular; DNA, Neoplasm; Female; Gene Frequency; Genomics - methods; High-Throughput Nucleotide Sequencing - methods; Humans; Life Sciences; Lymphoma - diagnosis; Lymphoma - genetics; Lymphoma - therapy; Magnetic Resonance Imaging; Male; Middle Aged; Mutation; Research Paper; Sensitivity and Specificity; circulating cell-free tumor DNA; somatic mutation; next-generation sequencing; liquid biopsy; primary central nervous system lymphoma
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.18325

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