Dataset Information

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

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.

SUBMITTER: Fontanilles M

PROVIDER: S-EPMC5564634 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Fontanilles Maxime M Marguet Florent F Bohers Élodie É Viailly Pierre-Julien PJ Dubois Sydney S Bertrand Philippe P Camus Vincent V Mareschal Sylvain S Ruminy Philippe P Maingonnat Catherine C Lepretre Stéphane S Veresezan Elena-Liana EL Derrey Stéphane S Tilly Hervé H Picquenot Jean-Michel JM Laquerrière Annie A Jardin Fabrice F

Oncotarget 20170701 29

<h4>Purpose</h4>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).<h4>Patients and methods</h4>PlasmacfDNA and matched tumor DNA (tDNA) from 25 PCNSL patients were sequenced using an Ion Torrent Personal Genome Machine (Life Technologies®). ...[more]

PMID: 28636991

Similar Datasets

Project description:INTRODUCTION:Multiple primary melanomas (MPM) occur up to 8% of patients with cutaneous malignant melanoma (CMM). They are often sporadic harbouring several somatic mutations, but also familial cases harbouring a CDKN2A germline mutation have been describe in Caucasian populations. The aim of this study was to investigate the incidence, the distribution patterns and the impact of known and unknown germline and somatic mutations in patients with MPM from Italy. MATERIALS AND METHODS:One-hundred and two MPM patients were enrolled for germline mutation analysis, and five patients with at least four MPMs were identified for somatic mutation analysis. The demographic, pathologic and clinical features were retrieved from medical records. Molecular analysis for both germline and somatic mutations was performed in genomic DNA from peripheral blood and tissue samples, respectively, through a next generation sequencing approach, using a specific multiple-gene panel constructed by the Italian Melanoma Intergroup for somatic analysis and a commercial cancer hotspot panel for somatic analysis. RESULTS:CDKN2A mutations were detected in 6/16 (37.5%) and 3/86 (3.5%) MPM cases with and without family history for melanoma, respectively. Furthermore, multiple MC1R and, to a lesser extent, ATM variants have been identified. BAP1 variants were found only in MPM patients from southern Italy. The most frequent somatic variants were the pathogenic BRAFV600E and TP53, followed by KIT, PIK3CA, KDR, and NRAS. Single APC, ERBB4, MET, JAK3 and other variants with unknown function were also detected. CONCLUSIONS:CDNK2A mutation is the most relevant susceptibility mutation in Italian patients with MPM, especially those with a family history for CMM. The prevalence of this mutation and other sequence variants identified in this study varies among specific sub-populations. Furthermore, some heterogeneity in driver somatic mutations between sporadic MPMs has been observed, as well as in a number of associated sequence variants the clinical impact of which needs to be further elucidated.

Project description:BackgroundsThe incidence of angiostrongyliasis is increasing in recent decades due to the expanding endemic areas all over the world. Clinicians face tremendous challenge of diagnosing angiostrongyliasis because of the lack of awareness of the disease and less effective definitive laboratory tests.Case presentationA 27-year-old man initially manifested skin itching, emesis, myalgia and quadriparesis. With progressive weakness of four limbs and elevated protein in the cerebrospinal fluid (CSF), he was diagnosed as Guillain-Barré syndrome and treated with intravenous methylprednisolone and immunoglobulin. However, the patient deteriorated with hyperpyrexia, headache and then persistent coma. The routine tests for Angiostrongylus cantonensis (A. cantonensis) with both the CSF and the serum were all negative. In contrast, the metagenomic next-generation sequencing (mNGS) was applied with the serum sample and the CSF sample in the middle phase. The central nervous system (CNS) angiostrongyliasis was diagnosed by mNGS with the mid-phase CSF, but not the mid-phase serum. At the same time, the CSF analysis revealed eosinophils ratio up to 67%. The discovery of A. cantonensis was confirmed by PCR with CSF later. Unfortunately, the patient died of severe angiostrongyliasis. During his hospitalization, mNGS was carried out repeatedly after definitive diagnosis and targeted treatment. The DNA strictly map reads number of A. cantonensis detected by mNGS was positively correlated with the CSF opening pressure and clinical manifestations.ConclusionsThe case of A. cantonensis infection highlights the benefit of mNGS as a target-free identification in disclosing the rare CNS angiostrongyliasis in the unusual season, while solid evidence from routine clinical testing was absent. The appropriate sample of mNGS should be chosen according to the life cycle of A. cantonensis. Besides, given the fact that the DNA reads number of A. cantonensis fluctuated with CSF opening pressure and clinical manifestations, whether mNGS could be applied as a marker of effectiveness of treatment is worth further exploration.

Dataset Information

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

Purpose

Patients and methods

Results

Conclusion

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets