Addition of chromosomal microarray and next generation sequencing to FISH and classical cytogenetics enhances genomic profiling of myeloid malignancies
| Autor: | Kristina J. Fasig, Patrick A. Lennon, Dana Tunnel, Terence Casey, Matthew Andreatta, Vladimir Kravtsov, Ian W. Flinn, Malini Sathanoori, James L. Prescott, Pranil Chandra, Scott R. Wheeler, David C. Spence, Zeq Ma, Randall Woodford, Sandeep Mukherjee, Hao Ho, Heather Rietz, Christopher D. Coldren, Mick Correll, Natalia Kozyr, Jesus G. Berdeja, William Donnelan, Mark Bouzyk, Taylor Hartley |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Cancer Research Myeloid Microarray DNA Copy Number Variations Biology DNA sequencing Cohort Studies 03 medical and health sciences Cytogenetics 0302 clinical medicine medicine Genetics Chromosomes Human Humans Copy-number variation Molecular Biology In Situ Hybridization Fluorescence Oligonucleotide Array Sequence Analysis Myeloproliferative Disorders medicine.diagnostic_test High-Throughput Nucleotide Sequencing Genomics Human genetics Tumor Burden 030104 developmental biology medicine.anatomical_structure DNA profiling 030220 oncology & carcinogenesis Mutation Fluorescence in situ hybridization |
| Zdroj: | Cancer genetics. |
| ISSN: | 2210-7762 |
| Popis: | Comprehensive genetic profiling is increasingly important for the clinical workup of hematologic tumors, as specific alterations are now linked to diagnostic characterization, prognostic stratification and therapy selection. To characterize relevant genetic and genomic alterations in myeloid malignancies maximally, we utilized a comprehensive strategy spanning fluorescence in situ hybridization (FISH), classical karyotyping, Chromosomal Microarray (CMA) for detection of copy number variants (CNVs) and Next generation Sequencing (NGS) analysis. In our cohort of 569 patients spanning the myeloid spectrum, NGS and CMA testing frequently identified mutations and copy number changes in the majority of genes with important clinical associations, such as TP53, TET2, RUNX1, SRSF2, APC and ATM. Most importantly, NGS and CMA uncovered medically actionable aberrations in 75.6% of cases normal by FISH/cytogenetics testing. NGS identified mutations in 65.5% of samples normal by CMA, cytogenetics and FISH, whereas CNVs were detected in 10.1% cases that were normal by all other methodologies. Finally, FISH or cytogenetics, or both, were abnormal in 14.1% of cases where NGS or CMA failed to detect any changes. Multiple mutations and CNVs were found to coexist, with potential implications for patient stratification. Thus, high throughput genomic tumor profiling through targeted DNA sequencing and CNV analysis complements conventional methods and leads to more frequent detection of actionable alterations. |
| Databáze: | OpenAIRE |
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