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      Genomic heterogeneity of multiple synchronous lung cancer

      research-article
      1 , 2 , 3 , 1 , 4 , 5 , 6 , 4 , 2 , 7 , 4 , 6 , 8 , 9 , 7 , 6 , 1 , 6 , 7 , 4 , 7 , 8 , 1 , 1 , 1 , 5 , 5 , 5 , 5 , 10 , 1 , 5 , 11 , 12 , 13 , 13 , 13 , 3 , 3 , 3 , 12 , 13 , 5 , 14 , 4 , 8 , a , 2 , 15 , b , 1
      Nature Communications
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          Abstract

          Multiple synchronous lung cancers (MSLCs) present a clinical dilemma as to whether individual tumours represent intrapulmonary metastases or independent tumours. In this study we analyse genomic profiles of 15 lung adenocarcinomas and one regional lymph node metastasis from 6 patients with MSLC. All 15 lung tumours demonstrate distinct genomic profiles, suggesting all are independent primary tumours, which are consistent with comprehensive histopathological assessment in 5 of the 6 patients. Lung tumours of the same individuals are no more similar to each other than are lung adenocarcinomas of different patients from TCGA cohort matched for tumour size and smoking status. Several known cancer-associated genes have different mutations in different tumours from the same patients. These findings suggest that in the context of identical constitutional genetic background and environmental exposure, different lung cancers in the same individual may have distinct genomic profiles and can be driven by distinct molecular events.

          Abstract

          Some patients present with multiple lung tumours but it is unclear whether these are metastases or individual lesions. Here, the authors use genomics techniques to demonstrate in six patients that multiple tumours have individual genetic profiles and represent separate tumours.

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          Most cited references17

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          Genome Remodeling in a Basal-like Breast Cancer Metastasis and Xenograft

          Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumor progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumor, a brain metastasis, and a xenograft derived from the primary tumor. The metastasis contained two de novo mutations and a large deletion not present in the primary tumor, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumor mutations, and displayed a mutation enrichment pattern that paralleled the metastasis (16 of 20 genes). Two overlapping large deletions, encompassing CTNNA1, were present in all three tumor samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared to the primary tumor suggest that secondary tumors may arise from a minority of cells within the primary.
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            Multiple primary lung cancers.

            Data on 50 patients with multiple separate primary carcinomas of the lung are presented. Eighteen had synchronous tumors and 32 had metachronous tumors, the intervals between diagnoses varying from 4 months to 16 years. Histologic patterns in the two different carcinomas were the same in 31 patients, most commonly epidermoid, and they were different in 19 patients. The problems involved in establishing the diagnosis of multiple primary lung cancers, the choice of treatment, and the expectation for survival are discussed.
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              • Article: not found

              Emerging patterns of somatic mutations in cancer.

              Recent advances in technological tools for massively parallel, high-throughput sequencing of DNA have enabled the comprehensive characterization of somatic mutations in a large number of tumour samples. In this Review, we describe recent cancer genomic studies that have assembled emerging views of the landscapes of somatic mutations through deep-sequencing analyses of the coding exomes and whole genomes in various cancer types. We discuss the comparative genomics of different cancers, including mutation rates and spectra, as well as the roles of environmental insults that influence these processes. We highlight the developing statistical approaches that are used to identify significantly mutated genes, and discuss the emerging biological and clinical insights from such analyses, as well as the future challenges of translating these genomic data into clinical impacts.
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                Author and article information

                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group
                2041-1723
                21 October 2016
                2016
                : 7
                : 13200
                Affiliations
                [1 ]State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences , Beijing 100021, People's Republic of China
                [2 ]Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center , 1515 Holcombe Boulevard, Houston, Texas 77030, USA
                [3 ]Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center , 1515 Holcombe Boulevard, Houston, Texas 77030, USA
                [4 ]Department of Pathology, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences , Beijing 100021, People's Republic of China
                [5 ]Beijing Genomics Institute , Shenzhen 518083, People's Republic of China
                [6 ]Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center , 1515 Holcombe Boulevard, Houston, Texas 77030, USA
                [7 ]Department of Diagnostic Imaging, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences , Beijing 100021, People's Republic of China
                [8 ]Department of Thoracic Surgical Oncology, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences , Beijing 100021, People's Republic of China
                [9 ]Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center , 1515 Holcombe Boulevard, Houston, Texas 77030, USA
                [10 ]State Key Laboratory of Molecular Oncology, Department of Cellular and Molecular Biology, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences , Beijing 100021, People's Republic of China
                [11 ]Department of Biostatistics, The University of Texas MD Anderson Cancer Center , 1515 Holcombe Boulevard, Houston, Texas 77030, USA
                [12 ]Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center , 1515 Holcombe Boulevard, Houston, Texas 77030, USA
                [13 ]Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center , 1515 Holcombe Boulevard, Houston, Texas 77030, USA
                [14 ]Department of Biology, University of Copenhagen , DK-2200 Copenhagen, Denmark
                [15 ]Honorary Faculty, Wellcome Trust Sanger Institute , Hinxton, Cambridgeshire CB10 1SA, UK
                Author notes
                [*]

                These authors contributed equally to this work

                [†]

                These authors jointly supervised this work

                Author information
                http://orcid.org/0000-0001-9526-6730
                http://orcid.org/0000-0003-4579-3959
                Article
                ncomms13200
                10.1038/ncomms13200
                5078731
                27767028
                d8d7df0e-3d46-4f64-9479-33170afd6330
                Copyright © 2016, The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 25 February 2016
                : 11 September 2016
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