Noninvasive genotyping and monitoring of anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer by capturebased next-generation sequencing

Ye Wang, Pan Wen Tian, Wei Ya Wang, Ke Wang, Zhou Zhang, Bo Jiang Chen, Yan Qi He, Lei Li, Hao Liu, Shannon Chuai, Wei Min Li*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Noninvasive genotyping of driver genes and monitoring of tumor dynamics help make better personalized therapeutic decisions. However, neither PCR-based assays nor amplicon-based targeted sequencing can detect fusion genes like anaplastic lymphoma kinase (ALK) rearrangements in blood samples. To investigate the feasibility and performance of capture-based sequencing on ALK fusion detection, we developed a capture-based targeted sequencing panel to detect and quantify rearrangement events, along with other driver mutation variants in plasma. In this perspective study, we screened 364 patients with advanced non-small cell lung cancer (NSCLC) for ALK rearrangements, and collected blood samples from 24 of them with confirmed ALK rearrangements based on their tissue biopsies. ALK rearrangements were successfully detected in 19 of 24 patients at baseline with 79.2% (95% CI 57.9%, 92.9%) sensitivity and 100% (36/36) specificity. Among the 24 patients, we obtained longitudinal blood samples from 7 of them after either chemotherapy and/or Crizotinib treatment for disease monitoring. The by-sample detection rate of ALK rearrangements after treatment drops to 69.2% (9 of 13). In addition to detecting ALK rearrangements, we also detected 3 Crizotinib resistant mutations, ALK L1152R, ALK I1171T and ALK L1196M from patient P4. ctDNA concentration correlates with responses and disease progression, reflecting its ability as a biomarker. Our findings suggest capture-based sequencing can detect and quantify ALK rearrangements as well as other somatic mutations, including mutations mediated drug resistance, in plasma with high sensitivity, paving the way for its application in identifying driver fusion genes and monitoring tumor dynamics in the clinic.

Original languageEnglish (US)
Pages (from-to)65208-65217
Number of pages10
JournalOncotarget
Volume7
Issue number40
DOIs
StatePublished - 2016
Externally publishedYes

Keywords

  • ALK fusion
  • ALK rearrangements
  • Capture-based next-generation sequencing
  • Cell-free DNA
  • Non-small cell lung cancer

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Noninvasive genotyping and monitoring of anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer by capturebased next-generation sequencing'. Together they form a unique fingerprint.

Cite this