Circulating tumour DNA sequence analysis as an alternative to multiple myeloma bone marrow aspirates
| Autor: | Rayan Kaedbey, Arnavaz Danesh, Esther Masih-Khan, Jessica Liu, Tiantian Li, Signy Chow, Amit M. Oza, Suzanne Kamel-Reid, Zhihua Li, Suzanne Trudel, Scott V. Bratman, Olena Kis, Tong Zhang, Mark Mansour, Mark Dowar, Trevor J. Pugh |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Neuroblastoma RAS viral oncogene homolog Proto-Oncogene Proteins B-raf Class I Phosphatidylinositol 3-Kinases Biopsy Science General Physics and Astronomy Bone Marrow Cells Biology medicine.disease_cause Sensitivity and Specificity General Biochemistry Genetics and Molecular Biology Article Circulating Tumor DNA GTP Phosphohydrolases Proto-Oncogene Proteins p21(ras) 03 medical and health sciences 0302 clinical medicine Gene Frequency medicine Biomarkers Tumor Humans Liquid biopsy Allele frequency Multiple myeloma Alleles Multidisciplinary medicine.diagnostic_test High-Throughput Nucleotide Sequencing Membrane Proteins General Chemistry Sequence Analysis DNA medicine.disease ErbB Receptors 030104 developmental biology medicine.anatomical_structure DNA profiling 030220 oncology & carcinogenesis Immunology Mutation Cancer research KRAS Bone marrow Multiple Myeloma |
| Zdroj: | Nature Communications, Vol 8, Iss 1, Pp 1-11 (2017) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | The requirement for bone-marrow aspirates for genomic profiling of multiple myeloma poses an obstacle to enrolment and retention of patients in clinical trials. We evaluated whether circulating cell-free DNA (cfDNA) analysis is comparable to molecular profiling of myeloma using bone-marrow tumour cells. We report here a hybrid-capture-based Liquid Biopsy Sequencing (LB-Seq) method used to sequence all protein-coding exons of KRAS, NRAS, BRAF, EGFR and PIK3CA in 64 cfDNA specimens from 53 myeloma patients to >20,000 × median coverage. This method includes a variant filtering algorithm that enables detection of tumour-derived fragments present in cfDNA at allele frequencies as low as 0.25% (median 3.2%, range 0.25–46%). Using LB-Seq analysis of 48 cfDNA specimens with matched bone-marrow data, we detect 49/51 likely somatic mutations, with subclonal hierarchies reflecting tumour profiling (96% concordance), and four additional mutations likely missed by bone-marrow testing (>98% specificity). Overall, LB-Seq is a high fidelity adjunct to genetic profiling of bone-marrow in multiple myeloma. Genetic profiling of multiple myeloma requires painful bone marrow biopsies. Here, the authors develop an alternative non-invasive method for sequencing of five oncogenes in circulating cell-free DNA from myeloma patients, demonstrating 96% concordance with bone marrow tumour profiling results. |
| Databáze: | OpenAIRE |
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