ArticleNature communications2021
Enhanced specificity of clinical high-sensitivity tumor mutation profiling in cell-free DNA via paired normal sequencing using MSK-ACCESS.
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Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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120citing papers in PubMed
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120 citing papers in PubMed, 176 citations in OpenAlex.
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60 more citing papers are in PubMed but not listed here.
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Authors and funding
69 authors at 1 institution in 1 country.
A Rose Brannon *Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0003-4610-0149
Gowtham Jayakumaran *Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Monica DiosdadoDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-3475-9985
Juber PatelKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Anna RazumovaDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Yu HuDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Fanli MengKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Mohammad HaqueDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Justyna SadowskaDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Brian J MurphyDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Tessara BaldiDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Ian JohnsonKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-0353-1195
Ryan PtashkinDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Maysun HasanKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-6496-4752
Preethi SrinivasanKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Anoop Balakrishnan RemaDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0001-6104-5665
Ivelise RijoDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Aaron AgarunovDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Helen WonKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Dilmi PereraKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
David N BrownKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Aliaksandra SamoilaDepartment of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Xiaohong JingKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Erika GedvilaiteDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0003-1749-0045
Julie L YangKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0003-4747-6391
Dennis P StephensKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Jenna-Marie DixDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0001-8822-4049
Nicole DeGroatDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Khedoudja NafaDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Aijazuddin SyedDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Alan LiKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Emily S LebowDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Anita S BowmanDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-8651-5317
Donna C FergusonDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Ying LiuDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Douglas A MataDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Rohit SharmaDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Soo-Ryum YangDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Tejus BaleDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Jamal K BenhamidaDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0001-5542-9857
Jason C ChangDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Snjezana DoganDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Meera R HameedDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Jaclyn F HechtmanDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Christine MoungDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Dara S RossDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Efsevia VakianiDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Chad M VanderbiltDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-8114-0237
JinJuan YaoDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Pedram RazaviDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0003-4236-0576
Lillian M SmythDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-0986-9285
Sarat ChandarlapatyDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0003-4532-8053
Gopa IyerDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-5093-6099
Wassim AbidaDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
James J HardingDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Benjamin KrantzDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Eileen O'ReillyDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-8076-9199
Helena A YuDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Bob T LiDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0001-6661-8733
Charles M RudinDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0001-5204-3465
Luis DiazDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-7079-8914
David B SolitKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-6614-802X
Maria E ArcilaDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Marc LadanyiDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Brian LoomisKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-1863-1199
Dana TsuiDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Michael F BergerDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0003-3882-5000
Ahmet ZehirDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. zehira@mskcc.org.ORCID 0000-0001-5406-4104
Ryma BenayedDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. benayedr@mskcc.org.ORCID 0000-0002-3754-0321
Memorial Sloan Kettering Cancer Center · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MSPORE in Bladder CancerP50CA221745 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI OSTROVNAYA, IRINA · 2018 to 2024
$11.8MThe Impact of DNA Damage Repair Abnormalities in Prostate CancerP01CA228696 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI KANTOFF, PHILIP W · 2019 to 2024
$8.7MDefining mechanisms of resistance to hormonal therapy in breast cancerR01CA234361 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI CHANDARLAPATY, SARAT, SOLIT, DAVID B. · 2019 to 2023
$2.0MNCI NIH HHS P01 CA228696NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA221745NCI NIH HHS R01 CA234361
Abstract
Circulating cell-free DNA from blood plasma of cancer patients can be used to non-invasively interrogate somatic tumor alterations. Here we develop MSK-ACCESS (Memorial Sloan Kettering - Analysis of Circulating cfDNA to Examine Somatic Status), an NGS assay for detection of very low frequency somatic alterations in 129 genes. Analytical validation demonstrated 92% sensitivity in de-novo mutation calling down to 0.5% allele frequency and 99% for a priori mutation profiling. To evaluate the performance of MSK-ACCESS, we report results from 681 prospective blood samples that underwent clinical analysis to guide patient management. Somatic alterations are detected in 73% of the samples, 56% of which have clinically actionable alterations. The utilization of matched normal sequencing allows retention of somatic alterations while removing over 10,000 germline and clonal hematopoiesis variants. Our experience illustrates the importance of analyzing matched normal samples when interpreting cfDNA results and highlights the importance of cfDNA as a genomic profiling source for cancer patients.
Indexed as
Biomarkers, TumorCirculating Tumor DNADNA Mutational AnalysisGene FrequencyGenetic MarkersHigh-Throughput Nucleotide SequencingHumansMutationNeoplasmsBiomarkers, TumorCirculating Tumor DNAGenetic Markers
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