| Autor: |
Neeraj S. Salathia, Jian-Bing Fan, Gordon B. Mills, Funda Meric-Bernstam, John V. Heymach, Richard Shen, Chen Zhao, Jonathan Toung, Kristina M. Kruglyak, Han-Yu Chuang, Ravi Vijaya Satya, Sante Gnerre, Hyunsung J. Kim, Rajyalakshmi Luthra, E. Scott Kopetz, Milind Javle, Yue Zhao, Debra L. Andrews, Goran Cabrilo, Kiran Madwani, Nishma M. Ramzanali, Xuyu Cai, Siqing Fu, Daniel D. Karp, David S. Hong, Vivek Subbiah, Helen J. Huang, Li Liu, Jill Waters, Shile Zhang, Filip Janku |
| Rok vydání: |
2023 |
| Popis: |
Purpose: Tumor-derived cell-free DNA (cfDNA) in plasma can be used for molecular testing and provide an attractive alternative to tumor tissue. Commonly used PCR-based technologies can test for limited number of alterations at the time. Therefore, novel ultrasensitive technologies capable of testing for a broad spectrum of molecular alterations are needed to further personalized cancer therapy.Experimental Design: We developed a highly sensitive ultradeep next-generation sequencing (NGS) assay using reagents from TruSeqNano library preparation and NexteraRapid Capture target enrichment kits to generate plasma cfDNA sequencing libraries for mutational analysis in 61 cancer-related genes using common bioinformatics tools. The results were retrospectively compared with molecular testing of archival primary or metastatic tumor tissue obtained at different points of clinical care.Results: In a study of 55 patients with advanced cancer, the ultradeep NGS assay detected 82% (complete detection) to 87% (complete and partial detection) of the aberrations identified in discordantly collected corresponding archival tumor tissue. Patients with a low variant allele frequency (VAF) of mutant cfDNA survived longer than those with a high VAF did (P = 0.018). In patients undergoing systemic therapy, radiological response was positively associated with changes in cfDNA VAF (P = 0.02), and compared with unchanged/increased mutant cfDNA VAF, decreased cfDNA VAF was associated with longer time to treatment failure (TTF; P = 0.03).Conclusions: Ultradeep NGS assay has good sensitivity compared with conventional clinical mutation testing of archival specimens. A high VAF in mutant cfDNA corresponded with shorter survival. Changes in VAF of mutated cfDNA were associated with TTF. Clin Cancer Res; 23(18); 5648–56. ©2017 AACR. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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