EGAGenomicsOtherhttps://ega-archive.org/studies/EGAS00001000647EGAEGA study EGAS00001000647Title not providedEGArestrictedWe characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic intervention, including several personalized treatment approaches that are already in clinical evaluation. Marked differences in the pattern of genomic alterations existed between and within histological subtypes, thus challenging the original histomorphological diagnosis. Immunohistochemical studies confirmed many of these reassigned subtypes. The reassignment eliminated almost all cases of large cell carcinomas, some of which had therapeutically relevant alterations. Prospective testing of our genomics-based diagnostic algorithm in 5145 lung cancer patients enabled a genome-based diagnosis in 3863 (75%) patients, confirmed the feasibility of rational reassignments of large cell lung cancer, and led to improvement in overall survival in patients with EGFR-mutant or ALK-rearranged cancers. Thus, our findings provide support for broad implementation of genome-based diagnosis of lung cancer.A genomics-based classification of human lung tumors.Taxonomy, Genomics, human being, Man (Taxonomy), pulmo, Malignant Neoplasm, Malignancy, taxonomy, Comparative, Comparative Genomics, Neoplasms, Modern, Benign Neoplasm, Systematics, lung parenchyma, Benign Neoplasms, Cancers, Functional Genomics, Tumor, Malignant, human, Human, Neoplasias, Classifications, Taxonomies, hierarchies, Structural, hierarchy, Benign, Homo sapiens, pulmonary, parenchyma of lung, systematics, Modern Man, Functional, lung, Neoplasm, Structural Genomics, Lungs, Malignancies, neoplasm, Man, neoplasms, Neoplasia, Cancer, Tumors, Malignant Neoplasms.DER/faint little ball, Malignant tumor of lung, Antemortem Diagnosis, large cell carcinoma of the lung, Elp-B1, der, Elp-1, malignant tumor of lung, Errb1, malignant neoplasm of the lung, Tumor, Diagnosis, PIG61, mili, parenchyma of lung, epidermal growth factor-activated receptor activity, AI552599, symptoms, d-egf-r, Pulmonary cancer, treatment, Lung Cancer, lung large cell carcinoma, Genomes, Comparative Genomics, alveolar cell carcinoma, Large Cell Carcinomas, Lung Cancers, SURGICAL AND MEDICAL PROCEDURES, flb, Large Cell Carcinoma, resistance to, Malignant neoplasm of lung, disease management, Therapies, 9030024J15Rik, D-EGFR, Malignancies, somatic mutation, large cell lung carcinoma, Diagnose, NISBD2, Tumors, large cell undifferentiated lung carcinoma, anaplastic lung carcinoma, DER1, Therapy, close to, screening, Genomics, Lung cancer, pulmo, Elp, wide/broad, Wa5, l(2)09261, DEgfr, Comparative, lung parenchyma, Cancer of Lung, Functional Genomics, Procedure, somatic, CG10079, Diagnoses, DAlk, torpedo/egfr, Benign, Postmortem, Screenings, wa2, cancer of lung, Examinations and Diagnoses, Algorithm, dALK, Malignant lung tumor, malignant tumour of lung, Postmortem Diagnosis, neoplasms, Carcinomas, Diagnoses and Examination, egfr, Lung malignant tumors, Postmortem Diagnoses, malignant lung neoplasm, HD-33, El, adenocarcinoma of lung, DER/EGFR, EGFR, EGfr, EgfR, susceptibility to, dEgfr, signs, Benign Neoplasms, DER flb, whole genome, Torpedo/Egfr, Treatments, Malignant Neoplasms, Degfr, response to tyrosine kinase inhibitor in, wide, pulmonary, Patient, DEGFR, l(2)57DEFa, l(2)05351, dEGFR, Cancer of the Lung, lung neoplasm, DmHD-33, large cell lung cancer, Cancer of the lung, NBLST3, Lung, D-Egf, LCLC, C-erb, Neoplasms, malignant lung tumor, lung cancer, Benign Neoplasm, mor1, Cell Carcinoma, broad, mENA, EK2-6, Malignant, autosomal dominant, large cell carcinoma of lung, Intervention or Procedure, Cell Carcinomas, Structural, c-erbB, EGFr, Egfr, CG8250, lung, Mass, Functional, Tcrz, Screening, torpedo/Egfr, EGF receptor activity, TOP, Egf-r, Antemortem, Pulmonary Cancer, neoplasm, Pulmonary, EGF-R, malignant tumour of the lung, Large, pattern, Malignancy, interventionDescription, distribution, LNCR, Interventional, top, Torpedo/DER, Diagnoses and Examinations, top/flb, Neoplasias, Lung Neoplasm, l(2)57EFa, malignant neoplasm of lung, Clients, l(2)57Ea, DmelCG8250, Cancer, Elp-B1RB1, ALK, Intervention Strategies, Antemortem Diagnoses, Pulmonary Neoplasms, findings, Malignant Neoplasm, DAlk53, TGF-alpha receptor activity, ERBB, dEGFR1, Client, Examination and Diagnoses, near to, epidermal growth factor receptor activity, DmelCG10079, Mass Screenings, Neoplasm, malignant lung tumour, Nonsmall cell lung cancer, DER/top, Large Cell, Intervention, malignant tumor of the lung, top/DER, Pulmonary Neoplasm, ERBB1, Cancers, wa-2, somatic., Egf, nonsmall cell lung cancer, EFG-R, Therapeutic, Errp, approaches, Erbb, vicinity of, Der, DER, protection against, Treatment, Structural Genomics, Lungs, Pulmonary Cancers, transforming growth factor-alpha receptor activity, Neoplasia, DER/torpedo, CD246, HER1Taxonomy, Genomics, human being, Man (Taxonomy), pulmo, Malignant Neoplasm, Malignancy, taxonomy, Comparative, Comparative Genomics, Neoplasms, Modern, Benign Neoplasm, Systematics, lung parenchyma, Benign Neoplasms, Cancers, Functional Genomics, Tumor, Malignant, human, Human, Neoplasias, Classifications, Taxonomies, hierarchies, Structural, hierarchy, Benign, Homo sapiens, pulmonary, parenchyma of lung, systematics, Modern Man, Functional, lung, Neoplasm, Structural Genomics, Lungs, Malignancies, neoplasm, Man, neoplasms, Neoplasia, Cancer, Tumors, Malignant Neoplasms.DER/faint little ball, Malignant tumor of lung, Antemortem Diagnosis, large cell carcinoma of the lung, Elp-B1, der, Elp-1, malignant tumor of lung, Errb1, malignant neoplasm of the lung, Tumor, Diagnosis, PIG61, mili, parenchyma of lung, epidermal growth factor-activated receptor activity, AI552599, symptoms, d-egf-r, Pulmonary cancer, treatment, Lung Cancer, lung large cell carcinoma, Genomes, Comparative Genomics, alveolar cell carcinoma, Large Cell Carcinomas, Lung Cancers, SURGICAL AND MEDICAL PROCEDURES, flb, Large Cell Carcinoma, resistance to, Malignant neoplasm of lung, disease management, Therapies, 9030024J15Rik, D-EGFR, Malignancies, somatic mutation, large cell lung carcinoma, Diagnose, NISBD2, Tumors, large cell undifferentiated lung carcinoma, anaplastic lung carcinoma, DER1, Therapy, close to, screening, Genomics, Lung cancer, pulmo, Elp, wide/broad, Wa5, l(2)09261, DEgfr, Comparative, lung parenchyma, Cancer of Lung, Functional Genomics, Procedure, somatic, CG10079, Diagnoses, DAlk, torpedo/egfr, Benign, Postmortem, Screenings, wa2, cancer of lung, Examinations and Diagnoses, Algorithm, dALK, Malignant lung tumor, malignant tumour of lung, Postmortem Diagnosis, neoplasms, Carcinomas, Diagnoses and Examination, egfr, Lung malignant tumors, Postmortem Diagnoses, malignant lung neoplasm, HD-33, El, adenocarcinoma of lung, DER/EGFR, EGFR, EGfr, EgfR, susceptibility to, dEgfr, signs, Benign Neoplasms, DER flb, whole genome, Torpedo/Egfr, Treatments, Malignant Neoplasms, Degfr, response to tyrosine kinase inhibitor in, wide, pulmonary, Patient, DEGFR, l(2)57DEFa, l(2)05351, dEGFR, Cancer of the Lung, lung neoplasm, DmHD-33, large cell lung cancer, Cancer of the lung, NBLST3, Lung, D-Egf, LCLC, C-erb, Neoplasms, malignant lung tumor, lung cancer, Benign Neoplasm, mor1, Cell Carcinoma, broad, mENA, EK2-6, Malignant, autosomal dominant, large cell carcinoma of lung, Intervention or Procedure, Cell Carcinomas, Structural, c-erbB, EGFr, Egfr, CG8250, lung, Mass, Functional, Tcrz, Screening, torpedo/Egfr, EGF receptor activity, TOP, Egf-r, Antemortem, Pulmonary Cancer, neoplasm, Pulmonary, EGF-R, malignant tumour of the lung, Large, pattern, Malignancy, interventionDescription, distribution, LNCR, Interventional, top, Torpedo/DER, Diagnoses and Examinations, top/flb, Neoplasias, Lung Neoplasm, l(2)57EFa, malignant neoplasm of lung, Clients, l(2)57Ea, DmelCG8250, Cancer, Elp-B1RB1, ALK, Intervention Strategies, Antemortem Diagnoses, Pulmonary Neoplasms, findings, Malignant Neoplasm, DAlk53, TGF-alpha receptor activity, ERBB, dEGFR1, Client, Examination and Diagnoses, near to, epidermal growth factor receptor activity, DmelCG10079, Mass Screenings, Neoplasm, malignant lung tumour, Nonsmall cell lung cancer, DER/top, Large Cell, Intervention, malignant tumor of the lung, top/DER, Pulmonary Neoplasm, ERBB1, Cancers, wa-2, somatic., Egf, nonsmall cell lung cancer, EFG-R, Therapeutic, Errp, approaches, Erbb, vicinity of, Der, DER, protection against, Treatment, Structural Genomics, Lungs, Pulmonary Cancers, transforming growth factor-alpha receptor activity, Neoplasia, DER/torpedo, CD246, HER1falseA Genomics-Based Classification of Human Lung TumorsWe characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic intervention, including several personalized treatment approaches that are already in clinical evaluation. Marked differences in the pattern of genomic alterations existed between and within histological subtypes, thus challenging the original histomorphological diagnosis. Immunohistochemical studies confirmed many of these reassigned subtypes. The reassignment eliminated almost all cases of large cell carcinomas, some of which had therapeutically relevant alterations. Prospective testing of our genomics-based diagnostic algorithm in 5145 lung cancer patients enabled a genome-based diagnosis in 3863 (75%) patients, confirmed the feasibility of rational reassignments of large cell lung cancer, and led to improvement in overall survival in patients with EGFR-mutant or ALK-rearranged cancers. Thus, our findings provide support for broad implementation of genome-based diagnosis of lung cancer.2019-10-01 16:42:24EGAS00001000647960624174329EGAD00010000554EGAD00010000556EGAC00001000064