{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"technology_type":["Illumina HiSeq 2000"],"study_type":["Other"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001000930"],"host":["EGA"],"description":["EGA study EGAS00001000930"],"dataset_title":["TCS validation of 11 lung adenos","WES data"],"category":["restricted"],"repository":["EGA"],"pubmed_abstract":["Cancers are composed of populations of cells with distinct molecular and phenotypic features, a phenomenon termed intratumor heterogeneity (ITH). ITH in lung cancers has not been well studied. We applied multiregion whole-exome sequencing (WES) on 11 localized lung adenocarcinomas. All tumors showed clear evidence of ITH. On average, 76% of all mutations and 20 out of 21 known cancer gene mutations were identified in all regions of individual tumors, which suggested that single-region sequencing may be adequate to identify the majority of known cancer gene mutations in localized lung adenocarcinomas. With a median follow-up of 21 months after surgery, three patients have relapsed, and all three patients had significantly larger fractions of subclonal mutations in their primary tumors than patients without relapse. These data indicate that a larger subclonal mutation fraction may be associated with increased likelihood of postsurgical relapse in patients with localized lung adenocarcinomas."],"pubmed_title":["Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing."],"pubmed_authors":["Zhang Jianjun J, Fujimoto Junya J, Zhang Jianhua J, Wedge David C DC, Song Xingzhi X, Zhang Jiexin J, Seth Sahil S, Chow Chi-Wan CW, Cao Yu Y, Gumbs Curtis C, Gold Kathryn A KA, Kalhor Neda N, Little Latasha L, Mahadeshwar Harshad H, Moran Cesar C, Protopopov Alexei A, Sun Huandong H, Tang Jiabin J, Wu Xifeng X, Ye Yuanqing Y, William William N WN, Lee J Jack JJ, Heymach John V JV, Hong Waun Ki WK, Swisher Stephen S, Wistuba Ignacio I II, Futreal P Andrew PA"],"name_synonyms":["Adenocarcinoma, Carcinoma, Oxyphilic, localised, Malignant Neoplasm, pulmo, Adenomas, region or site annotation, Basal Cell, Neoplasms, Benign Neoplasm, Oxyphilic Adenocarcinoma, lung parenchyma, Tumor, Malignant, ADNOS, Adenocarcinomas, Granular Cell Adenocarcinomas, Benign, Tubular, Malignant Adenoma, parenchyma of lung, Granular Cell Adenocarcinoma, Neoplasm, lung, sequence, Tubular Carcinoma, Granular Cell, Oxyphilic Adenocarcinomas, Basal Cell Adenocarcinomas, neoplasm, Basal Cell Adenocarcinoma, neoplasms, Cribriform Carcinoma, Carcinomas, positional, localized, positional polypeptide feature, Malignancy, Adenoma, Granular Cell Carcinoma, Tubular Adenocarcinoma, Cribriform, Benign Neoplasms, Cancers, Tubular Carcinomas, Cribriform Carcinomas, Tubular Adenocarcinomas, Malignant Adenomas, Malignant Neoplasms, Neoplasias, geographical area, Granular Cell Carcinomas, pulmonary, heterogeneity, primary structure of sequence macromolecule., Malignancies, Lungs, other neoplasm, Neoplasia, Cancer, Tumors"],"pubmed_title_synonyms":["Adenocarcinoma, Carcinomas, Carcinoma, Oxyphilic, localised, localized, pulmo, Adenomas, Adenoma, Basal Cell, Granular Cell Carcinoma, Tubular Adenocarcinoma, Oxyphilic Adenocarcinoma, lung parenchyma, Cribriform, Tubular Carcinomas, Cribriform Carcinomas, Malignant, ADNOS, Adenocarcinomas, Tubular Adenocarcinomas, Malignant Adenomas, Granular Cell Adenocarcinomas, Tubular, Cribriform Carcinoma., Granular Cell Carcinomas, pulmonary, Malignant Adenoma, parenchyma of lung, heterogeneity, Granular Cell Adenocarcinoma, lung, Tubular Carcinoma, Lungs, Granular Cell, Oxyphilic Adenocarcinomas, Basal Cell Adenocarcinomas, neoplasm, Basal Cell Adenocarcinoma, neoplasms"],"description_synonyms":["scale tissue, Materials, Chromosomal Abnormalities, single-organism developmental process, determination, Adenomas, acetylglucosaminyltransferase-like protein, postnatal development, Cytogenetic Abnormality, Mbp1, growth and development, Tumor, ADNOS, Mutations, Techniques, ras, relapse, Abnormalities, sampling, parenchyma of lung, Method, Granular Cell Adenocarcinoma, Tubular Carcinoma, Whole Transcriptome, Transcriptome Sequencing, Relapses, cytopathology, myd, preoperative procedures, C-K-RAS, drug resistance, k-ras, Cribriform Carcinoma, rask2, imprinted and ancient gene protein, treatment, average, increased, Biopsies, like-acetylglucosaminyltransferase, Adenoma, Cytogenetic Abnormalities, Granular Cell Carcinoma, Complete Exome Sequencing, plant peltate hair, Whole Transcriptome Sequencing, Recurrences, Mbp-1, procedures, Tubular Carcinomas, geographical area, Methodological Studies, malignant neoplasm, disease management, Therapies, Malignancies, stage, thoracolumbar region, Tumors, Cytogenetic Aberrations, Therapy, Relapse, Carcinoma, anatomical protrusion, pulmo, gyltl1b-b, Ki-ras, Exome, lung parenchyma, Procedure, Adenocarcinomas, results, Chromosome Abnormality, Benign, Tubular, Malignant Adenoma, Recrudescence, MDDGA6, mKIAA0609, p21, Genetic Materials, median, Aberrations, KIAA0609, General, Basal Cell Adenocarcinoma, Aberration, neoplasms, Genetic Material, acetylglucosaminyltransferase-like 1A, Carcinomas, fg, Complete Transcriptome, gyltl1b, histopathology, positional polypeptide feature, follow up, mdc1d, Heterogeneity, Chromosome Abnormalities, Exomes, Cribriform, Benign Neoplasms, INSDC_feature:gene, Methodological, Methodological Study, LARGE_HUMAN, Treatments, Tubular Adenocarcinomas, Malignant Neoplasms, MDC1D, hyaline, enr, pulmonary, Chromosome, RASK2, Patient, Material, Autosome, spine, Whole Exome Sequencing, Cistron, other neoplasm, E430016J11Rik, Transcriptome Sequencings, accessory, invasive procedures, Adenocarcinoma, KI-RAS, whole exome, localised, Procedures, region or site annotation, Complete Exome, Neoplasms, impact-a., developmental stage, peltate hair, Abnormality, Kras2, NS3, drug susceptibility/resistance, Benign Neoplasm, Oxyphilic Adenocarcinoma, number, Gene, Autosome Abnormality, Surgery, Malignant, Ximpact, presence, LARGE1, supernumerary, froggy, Gyltl1a, Granular Cell Adenocarcinomas, protrusion, Chromosomal Aberrations, trunk, Genetic heterogeneity, Cytogenetic Aberration, lung, Studies, Kras-2, Basal Cell Adenocarcinomas, neoplasm, Technique, KRAS2, KRAS1, p21B, positional, WES, Complete, Exome Sequencings, Genetic, lateral shoot, localized, Malignancy, Recrudescences, MDDGB6, K-RAS4B, Tubular Adenocarcinoma, K-RAS4A, Chromosomal Abnormality, LARGE, Cribriform Carcinomas, Rumpf, Sequencing, Neoplasias, Study, BPFD#36, Whole Exome, torso, Granular Cell Carcinomas, Clients, Whole, heterogeneity, operative procedures, axillary shoot, Cancer, Oxyphilic, Malignant Neoplasm, Complete Exome Sequencings, Drug resistance, Basal Cell, K-RAS2B, Chromosome Aberration, K-RAS2A, K-ras, intraoperative procedures, c-Ki-ras, Cistrons, trunk region, Client, Chromosomal, development, Exome Sequencing, count in organism, MT, peroperative procedures, chemical analysis, Autosome Abnormalities, Neoplasm, Resistance, sequence, imprinted and ancient gene protein homolog, IMPACT, Granular Cell, Oxyphilic Adenocarcinomas, background, techniques, scales, AI929937, primary cancer, NS, Complete Transcriptome Sequencing, Cytogenetic, scale, increased number, operative therapy, response to drug, postnatal growth, Chromosomal Aberration, operations, Cancers, malignant tumor, primary structure of sequence macromolecule, Malignant Adenomas, introduction, Drug, present in greater numbers in organism, sample collection, clear, like-glycosyltransferase, Therapeutic, kras, CFC2, cardinality, perioperative procedures, Treatment, Lungs, assay, biopsy, growth, Neoplasia, RWDD5, methodology, glycosyltransferase-like protein LARGE1"],"pubmed_abstract_synonyms":["Adenocarcinoma, Recovery from surgery, localised, Materials, Complete Exome, Adenomas, region or site annotation, Neoplasms, Oxyphilic Adenocarcinoma, Benign Neoplasm, Gene, Tumor, composed of, Malignant, ADNOS, supernumerary, Granular Cell Adenocarcinomas, Mutations, relapse, parenchyma of lung, Granular Cell Adenocarcinoma, lung, Tubular Carcinoma, Whole Transcriptome, Transcriptome Sequencing, Relapses, Basal Cell Adenocarcinomas, neoplasm, Cribriform Carcinoma, average, increased, WES, positional, Complete, Exome Sequencings, localized, Genetic, Malignancy, Adenoma, Recrudescences, Granular Cell Carcinoma, Complete Exome Sequencing, Whole Transcriptome Sequencing, Recurrences, Tubular Adenocarcinoma, composition, Tubular Carcinomas, Cribriform Carcinomas, Sequencing, Neoplasias, geographical area, Whole Exome, Granular Cell Carcinomas, malignant neoplasm, Clients, Whole, heterogeneity, Malignancies, Cancer, Tumors, Relapse, Carcinoma, Oxyphilic, adequate, pulmo, Complete Exome Sequencings, Malignant Neoplasm, Basal Cell, Exome, lung parenchyma, compositionality, Cistrons, Adenocarcinomas, Client, Cell, Exome Sequencing, Tubular, Benign, MT, Malignant Adenoma, Recrudescence, Neoplasm, sequence, Genetic Materials, Granular Cell, median, Oxyphilic Adenocarcinomas, Basal Cell Adenocarcinoma, neoplasms, Genetic Material, Carcinomas, Complete Transcriptome, primary cancer, Complete Transcriptome Sequencing, positional polypeptide feature, distinct, increased number, content, follow up, Cribriform, Benign Neoplasms, INSDC_feature:gene, Cancers, malignant tumor, Tubular Adenocarcinomas, Malignant Adenomas, primary structure of sequence macromolecule, Malignant Neoplasms, present in greater numbers in organism, Cribriform Carcinoma., clear, hyaline, pulmonary, Patient, Material, structure, Whole Exome Sequencing, Cistron, Lungs, Transcriptome Sequencings, Neoplasia, accessory"],"additional_accession":[]},"is_claimable":false,"name":"Intra-tumor heterogeneity of localized lung adenocarcinomas defined by multi-region sequencing","description":"Background: Intra-tumor heterogeneity (ITH) may have profound impacts on biopsy strategy, characterization of actionable targets, treatment planning, and drug resistance. ITH of lung cancers has not been well studied.   Methods: We performed multi-region whole exome sequencing (average sequencing depth 277x) on 48 tumor regions from 11 resected lung adenocarcinomas (8 stage I, 2 stage II and one stage III tumors) followed by deep sequencing validation (average sequencing depth 863x).   Results: All tumors showed clear evidence of spatial ITH. On average, 76% of all mutations and 20/21 known cancer gene mutations were present in all regions of individual tumors (trunk mutations). Copy number analysis did not show substantial difference in large-scale chromosome aberrations. A canonical KRAS p.G12C mutation was detected in only 1 of 4 tumor regions (branch mutations) at exome depth but detected in all four tumor regions (trunk mutations) at increased sequencing depth. In addition, many heterogeneous branch mutations defined by exome sequencing were detectable in all regions of individual tumors with increasing sequencing depth. Significant differences in mutational spectrum were observed in 6 tumors indicating that specific mutational processes were likely operative at different times during development of these tumors. With a median follow up of 21 months post surgery, 3 patients have relapsed and all 3 patients presented with significantly larger fractions of subclonal mutations in their primary tumors.   Conclusions: Although multi-region sampling is still required to fully assess ITH complexity, single biopsy analysis at appropriate depth might be sufficient to identify the majority of known cancer gene mutations in localized lung adenocarcinomas. Larger subclonal mutation fractions may be associated with increased likelihood of postsurgical relapse in patients with localized lung adenocarcinomas. Studies on larger cohort, ideally with comprehensive clinical annotation and repeat biopsy at relapse are needed to fully understand the clinical impact of ITH.","dates":{"updated":"2017-07-26 15:39:25"},"accession":"EGAS00001000930","cross_references":{"TAXONOMY":["9606"],"pubmed":["25301631"],"EGA":["EGAD00001000985","EGAD00001000984","EGAC00001000223"]}}