학술논문
Enhanced specificity of clinical high-sensitivity tumor mutation profiling in cell-free DNA via paired normal sequencing using MSK-ACCESS
Document Type
Original Paper
Author
Rose Brannon, A.; Jayakumaran, Gowtham; Diosdado, Monica; Patel, Juber; Razumova, Anna; Hu, Yu; Meng, Fanli; Haque, Mohammad; Sadowska, Justyna; Murphy, Brian J.; Baldi, Tessara; Johnson, Ian; Ptashkin, Ryan; Hasan, Maysun; Srinivasan, Preethi; Rema, Anoop Balakrishnan; Rijo, Ivelise; Agarunov, Aaron; Won, Helen; Perera, Dilmi; Brown, David N.; Samoila, Aliaksandra; Jing, Xiaohong; Gedvilaite, Erika; Yang, Julie L.; Stephens, Dennis P.; Dix, Jenna-Marie; DeGroat, Nicole; Nafa, Khedoudja; Syed, Aijazuddin; Li, Alan; Lebow, Emily S.; Bowman, Anita S.; Ferguson, Donna C.; Liu, Ying; Mata, Douglas A.; Sharma, Rohit; Yang, Soo-Ryum; Bale, Tejus; Benhamida, Jamal K.; Chang, Jason C.; Dogan, Snjezana; Hameed, Meera R.; Hechtman, Jaclyn F.; Moung, Christine; Ross, Dara S.; Vakiani, Efsevia; Vanderbilt, Chad M.; Yao, JinJuan; Razavi, Pedram; Smyth, Lillian M.; Chandarlapaty, Sarat; Iyer, Gopa; Abida, Wassim; Harding, James J.; Krantz, Benjamin; O’Reilly, Eileen; Yu, Helena A.; Li, Bob T.; Rudin, Charles M.; Diaz, Luis; Solit, David B.; Arcila, Maria E.; Ladanyi, Marc; Loomis, Brian; Tsui, Dana; Berger, Michael F.; Zehir, Ahmet; Benayed, Ryma
Source
Nature Communications. 12(1)
Subject
Language
English
ISSN
2041-1723
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.
Liquid biopsies allow the non-invasive detection of somatic mutations from tumours. Here, the authors develop and test MSK-ACCESS, an NGS-based clinical assay for identifying low frequency mutations in 129 genes and describe how it benefits patients in the clinic.
Liquid biopsies allow the non-invasive detection of somatic mutations from tumours. Here, the authors develop and test MSK-ACCESS, an NGS-based clinical assay for identifying low frequency mutations in 129 genes and describe how it benefits patients in the clinic.