Format

Send to

Choose Destination
Oncotarget. 2017 Jul 18;8(29):48157-48168. doi: 10.18632/oncotarget.18325.

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

Author information

1
Department of Hematology, Cancer Center Henri Becquerel, 76000 Rouen, France.
2
INSERM U1245, Cancer Center Henri Becquerel, Institute of Research and Innovation in Biomedicine (IRIB), University of Normandy, UNIVROUEN, 76000 Rouen, France.
3
INSERM U1245 and Hôpital Charles Nicolle, NeoVasc Team, University of Normandy, UNIVROUEN, CHU-Hôpitaux de Rouen, 76031 Rouen, France.
4
Department of Neuropathology, Hôpital Charles Nicolle, Normandy Center for Genomic and Personalized Medicine, CHU-Hôpitaux de Rouen, 76031 Rouen, France.
5
Department of Pathology, Cancer Center Henri Becquerel, 76000 Rouen, France.
6
Department of Neurosurgery, Hôpital Charles Nicolle, CHU-Hôpitaux de Rouen, 76031 Rouen, France.

Abstract

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.

KEYWORDS:

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

PMID:
28636991
PMCID:
PMC5564634
DOI:
10.18632/oncotarget.18325
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center