| Autor: |
Jason C. Chang, Alan Li, Ian Johnson, Charles M. Rudin, David N Brown, Snjezana Dogan, Preethi Srinivasan, Julie L. Yang, Aijazuddin Syed, Meera Hameed, JinJuan Yao, Aaron Agarunov, Emily S. Lebow, Chad M. Vanderbilt, Christine Moung, Rohit Sharma, David B. Solit, Efsevia Vakiani, Anna Razumova, Bob T. Li, Monica Diosdado, James J. Harding, Mohammad Haque, Wassim Abida, Marc Ladanyi, Michael F. Berger, Anita S. Bowman, Dilmi Perera, Dennis Stephens, Luis A. Diaz, Brian J. Murphy, Benjamin A. Krantz, Maria E. Arcila, Tejus Bale, Ryan Ptashkin, Gopa Iyer, Helena A. Yu, Eileen M. O'Reilly, Angela Rose Brannon, Aliaksandra Samoila, Khedoudja Nafa, Dana Tsui, Maysun Hasan, Erika Gedvilaite, Sarat Chandarlapaty, Tessara Baldi, Lillian M. Smyth, Brian Houck-Loomis, Juber Patel, Yu Hu, Ryma Benayed, Helen Won, Ivelise Rijo, Nicole DeGroat, Jaclyn F. Hechtman, Douglas A. Mata, Justyna Sadowska, Dara S. Ross, Jamal Benhamida, Gowtham Jayakumaran, Ying Liu, Fanli Meng, Donna C. Ferguson, Pedram Razavi, Anoop Balakrishnan Rema, Ahmet Zehir, Soo-Ryum Yang, Xiaohong Jing, Jenna-Marie Dix |
| Rok vydání: |
2020 |
| Předmět: |
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| Popis: |
Circulating cell-free DNA (cfDNA) from blood plasma of cancer patients can be used to interrogate somatic tumor alterations non-invasively or when adequate tissue is unavailable. We have developed and clinically implemented MSK-ACCESS (Analysis of Circulating cfDNA to Evaluate Somatic Status), an NGS assay for detection of very low frequency somatic alterations in select exons and introns of 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 and utility of MSK-ACCESS, we report results from the first 681 prospective blood samples (617 patients) that underwent clinical analysis to guide patient management. Somatic mutations, copy number, and/or structural variants were detected in 73% of the samples, and 56% of these circulating-tumor DNA (ctDNA) positive samples had clinically actionable alterations. The utilization of matched white blood cell sequencing allowed retention of somatic alterations while filtering out over 10,000 germline and clonal hematopoiesis variants, thereby greatly enhancing the specificity of the assay. Taken together, our experience illustrates the importance of analyzing a matched normal sample when interpreting cfDNA results and highlights the potential of cfDNA profiling to guide treatment selection, monitor treatment response, and identify mechanisms of treatment resistance. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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