Predictive molecular pathology of lung cancer in Germany with focus on gene fusion testing: Methods and quality assurance

Abstract

Predictive molecular testing has become an important part of the diagnosis of any patient with lung cancer. Using reliable methods to ensure timely and accurate results is inevitable for guiding treatment decisions. In the past few years, parallel sequencing has been established for mutation testing, and its use is currently broadened for the detection of other genetic alterations, such as gene fusion and copy number variations. In addition, conventional methods such as immunohistochemistry and in situ hybridization are still being used, either for formalin‐fixed, paraffin‐embedded tissue or for cytological specimens. For the development and broad implementation of such complex technologies, interdisciplinary and regional networks are needed. The Network Genomic Medicine (NGM) has served as a model of centralized testing and decentralized treatment of patients and incorporates all German comprehensive cancer centers. Internal quality control, laboratory accreditation, and participation in external quality assessment is mandatory for the delivery of reliable results. Here, we provide a summary of current technologies used to identify patients who have lung cancer with gene fusions, briefly describe the structures of NGM and the national NGM (nNGM), and provide recommendations for quality assurance.

Challenges in diagnosis and biomarker testing for RET-altered lung and thyroid cancer care: an international mixed-method study

“…Novel educational resources and early outreach may be beneficial and practical for pathologists, as pathologists in this study did not always consider clinical trial data useful to their practice, with the notable exception of Germany. This might be explained by the fact that the German Society of Pathology and the Federal Association of German Pathologists have an Independent Quality Assurance initiative which constantly update relevant information for the pathology community [ 46 , 47 ]. Anticipated innovations and upcoming treatments could be a feature of a rigorously updated decision-making aid to assist pathologists in their role that also outlines the parameters of national regulations and reimbursement practices.…”

Overview of Molecular Detection Technologies for MET in Lung Cancer

“…DNA-based hybrid-capture NGS approaches that can detect both mutations and fusions have proven to be unreliable in the past and often lead to false negative results for fusion detection, especially in cases of novel fusions. This is due to the localization of fusion breakpoints in large intronic regions with repetitive sequences, which are difficult to cover using capture probes [35,54,69].…”

Targeted RNA-sequencing for the evaluation of gene fusions in lung tumors: current status and future prospects

“…However, there are not antibodies for all clinically relevant fusions. Additionally this approach has a high rate of false positive events and a second method is needed to verify fusions found by IHC [1].…”

“…RNA-Seq can be achieved by either comprehensive whole transcriptome-or targeted approaches [1]. Both allow the expression analysis of a defined gene set.…”