OBJECTIVE: To develop an easy-to-use technique for EML4-ALK detection and establish the effective selection of candidates for screening. BACKGROUND: We previously reported clinicopathological findings of patients with lung cancer harboring the EML4-ALK fusion gene. Anaplastic lymphoma kinase inhibitors have therapeutic effects in lung cancer patients with EML4-ALK, accounting for merely 1%-5% of lung cancers. METHODS: We investigated EML4-ALK in tumors from 581 patients. EML4-ALK was detected by a reverse transcription polymerase-chain reaction and by the newly established criteria and algorithm using a fluorescence in situ hybridization method. To establish an algorithm to restrict candidates chosen for ALK fusion gene detection, clinicopathological findings as well as EGFR, ERBB2, and KRAS mutations were analyzed. RESULTS: 8 (1.3%) tumors had EML4-ALK, EGFR, KRAS, and ERBB2 mutations, which were mutually exclusive and were detected in 191 (32.8%), 56 (9.6%), and 11 (1.8%) tumors, respectively. We screened 581 patients with tumors and another 27 who were nonsmokers or mild smokers (<20 packs per year) lacking EGFR, KRAS, and ERBB2 mutations and who had adenocarcinomas exhibiting an acinar component with moderate or poor differentiation. Of the 27 patients, 8 (29.6%) had EML4-ALK. CONCLUSIONS: We propose criteria for selecting candidates for efficient detection of the fusion gene.
OBJECTIVE: To develop an easy-to-use technique for EML4-ALK detection and establish the effective selection of candidates for screening. BACKGROUND: We previously reported clinicopathological findings of patients with lung cancer harboring the EML4-ALK fusion gene. Anaplastic lymphoma kinase inhibitors have therapeutic effects in lung cancerpatients with EML4-ALK, accounting for merely 1%-5% of lung cancers. METHODS: We investigated EML4-ALK in tumors from 581 patients. EML4-ALK was detected by a reverse transcription polymerase-chain reaction and by the newly established criteria and algorithm using a fluorescence in situ hybridization method. To establish an algorithm to restrict candidates chosen for ALK fusion gene detection, clinicopathological findings as well as EGFR, ERBB2, and KRAS mutations were analyzed. RESULTS: 8 (1.3%) tumors had EML4-ALK, EGFR, KRAS, and ERBB2 mutations, which were mutually exclusive and were detected in 191 (32.8%), 56 (9.6%), and 11 (1.8%) tumors, respectively. We screened 581 patients with tumors and another 27 who were nonsmokers or mild smokers (<20 packs per year) lacking EGFR, KRAS, and ERBB2 mutations and who had adenocarcinomas exhibiting an acinar component with moderate or poor differentiation. Of the 27 patients, 8 (29.6%) had EML4-ALK. CONCLUSIONS: We propose criteria for selecting candidates for efficient detection of the fusion gene.
Authors: Todd Hembrough; Wei-Li Liao; Christopher P Hartley; Patrick C Ma; Vamsidhar Velcheti; Christopher Lanigan; Sheeno Thyparambil; Eunkyung An; Manish Monga; David Krizman; Jon Burrows; Laura J Tafe Journal: Clin Chem Date: 2015-11-19 Impact factor: 8.327