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Targeted therapies guided by molecular diagnostics have become a standard treatment of lung cancer. Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are currently used as the best predictive biomarkers for EGFR tyrosine kinase inhibitors and ALK inhibitors, respectively. Besides EGFR and ALK, the list of druggable genetic alterations has been growing, including ROS1 rearrangements, RET rearrangements, and MET alterations. In this situation, pathologists should carefully manage clinical samples for molecular testing and should do their best to quickly and accurately identify patients who will benefit from precision therapeutics. Here, we grouped molecular biomarkers of lung cancers into three categories-mutations, gene rearrangements, and amplifications-and propose expanded guidelines on molecular testing of lung cancers.
Key Words: Lung neoplasms; Molecular testing; Guideline; Precision medicine
Molecular diagnostics-guided targeted therapies have become a standard treatment for patients with lung cancer.1 Driver genetic alterations such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are currently used as predictive biomarkers for EGFR tyrosine kinase inhibitors (TKIs) and ALK inhibitors, respectively.1 Since Korean guideline recommendations for EGFR and ALK molecular testing were published,2,3 the list of druggable genetic alterations has been growing as tremendous amounts of information on the cancer genome are becoming available (Table 1).4"6 Molecular analyses of various biomarkers in tumor tissue or cytology specimens have become standard laboratory tests for the clinical management of lung cancers. In this context, an updated and more comprehensive set of guidelines is necessary.
In this article, we propose expanded guidelines for molecular testing of lung cancers including recently updated genetic alterations and well-known biomarkers. Here, we grouped molecular biomarkers into three categories-mutations, gene rearrangements, and amplifications (Fig. 1)-and reviewed the background, indications, methods, reporting, test validations, and quality assurance for each category.
MOLECULAR TESTING
Mutations including EGFR, KRAS, BRAF, HER2, and MET
Background
Activating somatic mutations including point substitution, small insertion, and in-frame deletion are major oncogenic drivers in lung cancer. The discovery of activating EGFR mutations and their close relation with the response to EGFR TKIs opened the new era of precision medicine. Since then, clinical trials have confirmed that EGFR mutations are the best predictive factor of EGFR TKI efficacy.7,8 EGFR mutations have been more frequently found in lung adenocarcinomas in...