Capture-based next-generation sequencing reveals multiple actionable mutations in cancer patients failed in traditional testing

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Background:
Targeted therapies including monoclonal antibodies and small molecule inhibitors have dramatically changed the treatment of cancer over past 10 years. Their therapeutic advantages are more tumor specific and with less side effects. For precisely tailoring available targeted therapies to each individual or a subset of cancer patients, next-generation sequencing (NGS) has been utilized as a promising diagnosis tool with its advantages of accuracy, sensitivity, and high throughput.

Methods:
We developed and validated a NGS-based cancer genomic diagnosis targeting 115 prognosis and therapeutics relevant genes on multiple specimen including blood, tumor tissue, and body fluid from 10 patients with different cancer types. The sequencing data was then analyzed by the clinical-applicable analytical pipelines developed in house.

Results:
We have assessed analytical sensitivity, specificity, and accuracy of the NGS-based molecular diagnosis. Also, our developed analytical pipelines were capable of detecting base substitutions, indels, and gene copy number variations (CNVs). For instance, several actionable mutations of EGFR, PIK3CA,TP53, and KRAS have been detected for indicating drug susceptibility and resistance in the cases of lung cancer.

Conclusion:
Our study has shown that NGS-based molecular diagnosis is more sensitive and comprehensive to detect genomic alterations in cancer, and supports a direct clinical use for guiding targeted therapy.

Keywords:
Next-generation sequencing, molecular diagnosis, cancer panel, targeted therapy.

Autoři: Jing Xie ^1,2; †; Xiongxiong Lu ^1,3; †; Xue Wu ⁴; Xiaoyi Lin ⁵; Chao Zhang ⁴; Xiaofang Huang ⁴; Zhili Chang ⁴; Xinjing Wang ^1,3,6; Chenlei Wen ^1,3,6; Xiaomei Tang ^1,3,6; Minmin Shi ^1,3,6; Qian Zhan ^1,3; Hao Chen ^1,3,6; Xiaxing Deng ^1,3,6; Chenghong Peng ^1,3,6; Hongwei Li ³; Yuan Fang ^1,3,6,*; Yang Shao ^4,7,*; Baiyong Shen ^1,3,6,*
Působiště autorů: Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China ¹; Department of Pathology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China ²; Pancreatic Disease Centre, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China ³; Department of Research and Development, Geneseeq Technology Inc., Toronto, Ontario, Canada ⁴; Department of Laboratory Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China ⁵; Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China ⁶; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada ⁷
Vyšlo v časopise: Molecular Genetics & Genomic Medicine 2016; 4(3)
Kategorie: Original article
prolekare.web.journal.doi_sk: https://doi.org/10.1002/mgg3.201

© 2016 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Souhrn

Keywords:
Next-generation sequencing, molecular diagnosis, cancer panel, targeted therapy.

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