A novel break site of EML4-ALK report and a rare PRKAR1A-ALK report analyzed by different ALK detection platforms in non-small cell lung cancer patients

Thorac Cancer. 2021 Oct;12(20):2773-2779. doi: 10.1111/1759-7714.14123. Epub 2021 Sep 6.

Abstract

Background: detection of anaplastic lymphoma receptor tyrosine kinase gene (ALK) rearrangements in patients with non-small-cell lung cancer (NSCLC) has become a routine pathological diagnosis worldwide.

Methods: there are three major conventional diagnostic methods for ALK fusions: fluorescent in situ hybridization (FISH); immunohistochemistry (Ventana IHC (D5F3)); and polymerase chain reaction (PCR). Next-generation sequencing (NGS) technology as is a new tool for ALK status detection with great potential. These four methods are highly consistent in detecting ALK status (coincidence rate >96%). However, discrepancies in ALK status have been found in some patients among these methods, which causes confusion for clinicians.

Results and conclusion: in this study, we analyzed two patients whose ALK statuses were not consistent using these four methods. We explored the potential reasons for deviation of the test results and found a novel EML4-ALK break site, which had been not described previously.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaplastic Lymphoma Kinase / genetics*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Crizotinib / therapeutic use
  • Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / genetics
  • Female
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Immunohistochemistry / methods*
  • In Situ Hybridization, Fluorescence / methods*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics
  • Polymerase Chain Reaction / methods*

Substances

  • Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
  • EML4-ALK fusion protein, human
  • Oncogene Proteins, Fusion
  • PRKAR1A protein, human
  • Crizotinib
  • ALK protein, human
  • Anaplastic Lymphoma Kinase