当前位置： SCI文献检索 > Molecular Genetics & Genomic Medicine期刊下所有文献 > A novel molecular diagnostics platform for somatic and germline precision oncology.

A novel molecular diagnostics platform for somatic and germline precision oncology.

Abstract：

BACKGROUND:Next-generation sequencing (NGS) opens new options in clinical oncology, from therapy selection to genetic counseling. However, realization of this potential not only requires succeeding in the bioinformatics and interpretation of the results, but also in their integration into the clinical practice. We have developed a novel NGS diagnostic platform aimed at detecting (1) somatic genomic alterations associated with the response to approved targeted cancer therapies and (2) germline mutations predisposing to hereditary malignancies. METHODS:Next-generation sequencing libraries enriched in the exons of 215 cancer genes (97 for therapy selection and 148 for predisposition, with 30 informative for both applications), as well as selected introns from 17 genes involved in drug-related rearrangements, were prepared from 39 tumors (paraffin-embedded tissues/cytologies), 36 germline samples (blood) and 10 cell lines using hybrid capture. Analysis of NGS results was performed with specifically developed bioinformatics pipelines. RESULTS:The platform detects single-nucleotide variants (SNVs) and insertions/deletions (indels) with sensitivity and specificity >99.5% (allelic frequency ≥0.1), as well as copy-number variants (CNVs) and rearrangements. Somatic testing identified tailored approved targeted drugs in 35/39 tumors (89.74%), showing a diagnostic yield comparable to that of leading commercial platforms. A somatic EGFR p.E746_S752delinsA mutation in a mediastinal metastasis from a breast cancer prompted its anatomopathologic reassessment, its definite reclassification as a lung cancer and its treatment with gefitinib (partial response sustained for 15 months). Testing of 36 germline samples identified two pathogenic mutations (in CDKN2A and BRCA2). We propose a strategy for interpretation and reporting of results adaptable to the aim of the request, the availability of tumor and/or normal samples and the scope of the informed consent. CONCLUSION:With an adequate methodology, it is possible to translate to the clinical practice the latest advances in precision oncology, integrating under the same platform the identification of somatic and germline genomic alterations.

journal_name

Mol Genet Genomic Med

journal_title

Molecular genetics & genomic medicine

authors

Cabanillas R,Diñeiro M,Castillo D,Pruneda PC,Penas C,Cifuentes GA,de Vicente Á,Durán NS,Álvarez R,Ordóñez GR,Cadiñanos J

doi

10.1002/mgg3.291

subject

Has Abstract

pub_date

2017-04-23 00:00:00

pages

336-359

issue

issn

2324-9269

pii

MGG3291

journal_volume

pub_type

杂志文章

在线工具

A novel molecular diagnostics platform for somatic and germline precision oncology.