Genome-wide Sequencing of Cell-free DNA Enables Detection of Copy-number Alterations in Patients with Cancer Where Tissue Biopsy is Not Feasible
العنوان: | Genome-wide Sequencing of Cell-free DNA Enables Detection of Copy-number Alterations in Patients with Cancer Where Tissue Biopsy is Not Feasible |
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المؤلفون: | Graham McLennan, Amin Mazloom, Gregory A. Daniels, Daniel S. Grosu, Marcia Eisenberg, Razelle Kurzrock, Kimberly A. Holden, Shumei Kato, Prachi Nakashe, Kerry D. Fitzgerald, Eyad Almasri, Taylor J. Jensen, Christopher K. Ellison, Erin McCarthy, Lisa Kim, Aaron M. Goodman |
المصدر: | Molecular Cancer Therapeutics. 20:2274-2279 |
بيانات النشر: | American Association for Cancer Research (AACR), 2021. |
سنة النشر: | 2021 |
مصطلحات موضوعية: | Adult, Male, Genome instability, Oncology, Cancer Research, medicine.medical_specialty, DNA Copy Number Variations, Genome, Young Adult, Neoplasms, Internal medicine, Biomarkers, Tumor, medicine, Humans, In patient, Precision Medicine, Aged, Aged, 80 and over, Alternative methods, Autosome, Whole Genome Sequencing, business.industry, Cancer, Middle Aged, medicine.disease, Cell-free fetal DNA, Female, business, Cell-Free Nucleic Acids, Tissue biopsy |
الوصف: | When tissue biopsy is not medically prudent or tissue is insufficient for molecular testing, alternative methods are needed. Because cell-free DNA (cfDNA) has been shown to provide a representative surrogate for tumor tissue, we sought to evaluate its utility in this clinical scenario. cfDNA was isolated from the plasma of patients and assayed with low-coverage (∼0.3×), genome-wide sequencing. Copy-number alterations (CNA) were identified and characterized using analytic methods originally developed for noninvasive prenatal testing (NIPT) and quantified using the genomic instability number (GIN), a metric that reflects the quantity and magnitude of CNAs across the genome. The technical variability of the GIN was first evaluated in an independent cohort comprising genome-wide sequencing results from 27,754 women who consented to have their samples used for research and whose NIPT results yielded no detected CNAs to establish a detection threshold. Subsequently, cfDNA sequencing data from 96 patients with known cancers but for whom a tissue biopsy could not be obtained are presented. An elevated GIN was detected in 35% of patients and detection rates varied by tumor origin. Collectively, CNAs covered 96.6% of all autosomes. Survival was significantly reduced in patients with an elevated GIN relative to those without. Overall, these data provide a proof of concept for the use of low-coverage, genome-wide sequencing of cfDNA from patients with cancer to obtain relevant molecular information in instances where tissue is difficult to access. These data may ultimately serve as an informative complement to other molecular tests. |
تدمد: | 1538-8514 1535-7163 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fbb4571c5ecdc15463477fe226abb956Test https://doi.org/10.1158/1535-7163.mct-20-1066Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....fbb4571c5ecdc15463477fe226abb956 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15388514 15357163 |
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