ALBERT

Description: Cancers emerge from an ongoing Darwinian evolutionary process, often leading to multiple competing subclones within a single primary tumour. This evolutionary process culminates in the formation of metastases, which is the cause of 90% of cancer-related deaths. However, despite its clinical importance, little is known about the principles governing the dissemination of cancer cells to distant organs. Although the hypothesis that each metastasis originates from a single tumour cell is generally supported, recent studies using mouse models of cancer demonstrated the existence of polyclonal seeding from and interclonal cooperation between multiple subclones. Here we sought definitive evidence for the existence of polyclonal seeding in human malignancy and to establish the clonal relationship among different metastases in the context of androgen-deprived metastatic prostate cancer. Using whole-genome sequencing, we characterized multiple metastases arising from prostate tumours in ten patients. Integrated analyses of subclonal architecture revealed the patterns of metastatic spread in unprecedented detail. Metastasis-to-metastasis spread was found to be common, either through de novo monoclonal seeding of daughter metastases or, in five cases, through the transfer of multiple tumour clones between metastatic sites. Lesions affecting tumour suppressor genes usually occur as single events, whereas mutations in genes involved in androgen receptor signalling commonly involve multiple, convergent events in different metastases. Our results elucidate in detail the complex patterns of metastatic spread and further our understanding of the development of resistance to androgen-deprivation therapy in prostate cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413032/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413032/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gundem, Gunes -- Van Loo, Peter -- Kremeyer, Barbara -- Alexandrov, Ludmil B -- Tubio, Jose M C -- Papaemmanuil, Elli -- Brewer, Daniel S -- Kallio, Heini M L -- Hognas, Gunilla -- Annala, Matti -- Kivinummi, Kati -- Goody, Victoria -- Latimer, Calli -- O'Meara, Sarah -- Dawson, Kevin J -- Isaacs, William -- Emmert-Buck, Michael R -- Nykter, Matti -- Foster, Christopher -- Kote-Jarai, Zsofia -- Easton, Douglas -- Whitaker, Hayley C -- ICGC Prostate UK Group -- Neal, David E -- Cooper, Colin S -- Eeles, Rosalind A -- Visakorpi, Tapio -- Campbell, Peter J -- McDermott, Ultan -- Wedge, David C -- Bova, G Steven -- 077012/Wellcome Trust/United Kingdom -- A12758/Cancer Research UK/United Kingdom -- A14835/Cancer Research UK/United Kingdom -- CA92234/CA/NCI NIH HHS/ -- Cancer Research UK/United Kingdom -- Intramural NIH HHS/ -- England -- Nature. 2015 Apr 16;520(7547):353-7. doi: 10.1038/nature14347. Epub 2015 Apr 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK. ; 1] Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK [2] Department of Human Genetics, KU Leuven, Herestraat 49 Box 602, B-3000 Leuven, Belgium [3] Cancer Research UK London Research Institute, London WC2A 3LY, UK. ; 1] Norwich Medical School and Department of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK [2] The Genome Analysis Centre, Norwich NR4 7UH, UK. ; Institute of Biosciences and Medical Technology, BioMediTech, University of Tampere and Fimlab Laboratories, Tampere University Hospital, Tampere FI-33520, Finland. ; The James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA. ; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Maryland 20892, USA. ; University of Liverpool and HCA Pathology Laboratories, London WC1E 6JA, UK. ; Division of Genetics and Epidemiology, The Institute Of Cancer Research, London SW7 3RP, UK. ; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK. ; Uro-oncology Research Group, Cancer Research UK Cambridge Institute, Cambridge CB2 0RE, UK. ; 1] Uro-oncology Research Group, Cancer Research UK Cambridge Institute, Cambridge CB2 0RE, UK [2] Department of Surgical Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. ; 1] Norwich Medical School and Department of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK [2] Division of Genetics and Epidemiology, The Institute Of Cancer Research, London SW7 3RP, UK. ; 1] Division of Genetics and Epidemiology, The Institute Of Cancer Research, London SW7 3RP, UK [2] Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK; and Sutton SM2 5PT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25830880" target="_blank"〉PubMed〈/a〉

Description: Long interspersed nuclear element-1 (L1) retrotransposons are mobile repetitive elements that are abundant in the human genome. L1 elements propagate through RNA intermediates. In the germ line, neighboring, nonrepetitive sequences are occasionally mobilized by the L1 machinery, a process called 3' transduction. Because 3' transductions are potentially mutagenic, we explored the extent to which they occur somatically during tumorigenesis. Studying cancer genomes from 244 patients, we found that tumors from 53% of the patients had somatic retrotranspositions, of which 24% were 3' transductions. Fingerprinting of donor L1s revealed that a handful of source L1 elements in a tumor can spawn from tens to hundreds of 3' transductions, which can themselves seed further retrotranspositions. The activity of individual L1 elements fluctuated during tumor evolution and correlated with L1 promoter hypomethylation. The 3' transductions disseminated genes, exons, and regulatory elements to new locations, most often to heterochromatic regions of the genome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380235/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380235/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tubio, Jose M C -- Li, Yilong -- Ju, Young Seok -- Martincorena, Inigo -- Cooke, Susanna L -- Tojo, Marta -- Gundem, Gunes -- Pipinikas, Christodoulos P -- Zamora, Jorge -- Raine, Keiran -- Menzies, Andrew -- Roman-Garcia, Pablo -- Fullam, Anthony -- Gerstung, Moritz -- Shlien, Adam -- Tarpey, Patrick S -- Papaemmanuil, Elli -- Knappskog, Stian -- Van Loo, Peter -- Ramakrishna, Manasa -- Davies, Helen R -- Marshall, John -- Wedge, David C -- Teague, Jon W -- Butler, Adam P -- Nik-Zainal, Serena -- Alexandrov, Ludmil -- Behjati, Sam -- Yates, Lucy R -- Bolli, Niccolo -- Mudie, Laura -- Hardy, Claire -- Martin, Sancha -- McLaren, Stuart -- O'Meara, Sarah -- Anderson, Elizabeth -- Maddison, Mark -- Gamble, Stephen -- ICGC Breast Cancer Group -- ICGC Bone Cancer Group -- ICGC Prostate Cancer Group -- Foster, Christopher -- Warren, Anne Y -- Whitaker, Hayley -- Brewer, Daniel -- Eeles, Rosalind -- Cooper, Colin -- Neal, David -- Lynch, Andy G -- Visakorpi, Tapio -- Isaacs, William B -- van't Veer, Laura -- Caldas, Carlos -- Desmedt, Christine -- Sotiriou, Christos -- Aparicio, Sam -- Foekens, John A -- Eyfjord, Jorunn Erla -- Lakhani, Sunil R -- Thomas, Gilles -- Myklebost, Ola -- Span, Paul N -- Borresen-Dale, Anne-Lise -- Richardson, Andrea L -- Van de Vijver, Marc -- Vincent-Salomon, Anne -- Van den Eynden, Gert G -- Flanagan, Adrienne M -- Futreal, P Andrew -- Janes, Sam M -- Bova, G Steven -- Stratton, Michael R -- McDermott, Ultan -- Campbell, Peter J -- 088340/Wellcome Trust/United Kingdom -- 091730/Wellcome Trust/United Kingdom -- 14835/Cancer Research UK/United Kingdom -- C5047/A14835/Cancer Research UK/United Kingdom -- G0900871/Medical Research Council/United Kingdom -- P30 CA006973/CA/NCI NIH HHS/ -- WT100183MA/Wellcome Trust/United Kingdom -- Department of Health/United Kingdom -- New York, N.Y. -- Science. 2014 Aug 1;345(6196):1251343. doi: 10.1126/science.1251343.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK. ; Department of Physiology, School of Medicine-Center for Resesarch in Molecular Medicine and Chronic Diseases, Instituto de Investigaciones Sanitarias, University of Santiago de Compostela, Spain. ; Lungs for Living Research Centre, Rayne Institute, University College London (UCL), London, UK. ; Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK. Department of Clinical Science, University of Bergen, Bergen, Norway. Department of Oncology, Haukeland University Hospital, Bergen, Norway. ; Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK. Human Genome Laboratory, Department of Human Genetics, VIB and KU Leuven, Leuven, Belgium. ; Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK. Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, UK. ; Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK. Department of Haematology, University of Cambridge, Cambridge, UK. ; University of Liverpool and HCA Pathology Laboratories, London, UK. ; Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, UK. ; Cancer Research UK (CRUK) Cambridge Institute, University of Cambridge, Cambridge, UK. ; Institute of Cancer Research, Sutton, London, UK. University of East Anglia, Norwich, UK. ; Institute of Cancer Research, Sutton, London, UK. ; Institute of Biosciences and Medical Technology-BioMediTech, University of Tampere and Tampere University Hospital, Tampere, Finland. ; Johns Hopkins University, Baltimore, MD, USA. ; Netherlands Cancer Institute, Amsterdam, Netherlands. ; Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium. ; British Columbia Cancer Agency, Vancouver, Canada. ; Department of Medical Oncology, Erasmus Medical Center Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands. ; Cancer Research Laboratory, University of Iceland, Reykjavik, Iceland. ; School of Medicine, University of Queensland, Brisbane, Australia. Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane, Australia. UQ Centre for Clinical Research, University of Queensland, Brisbane, Australia. ; Universite Lyon 1, Institut National du Cancer (INCa)-Synergie, Lyon, France. ; Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. ; Department of Radiation Oncology and Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, Netherlands. ; Dana-Farber Cancer Institute, Boston, MA, USA. ; Department of Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands. ; Institut Bergonie, 229 cours de l'Argone, 33076 Bordeaux, France. Institut Curie, Department of Tumor Biology, 26 rue d'Ulm, 75248 Paris cedex 05, France. ; Translational Cancer Research Unit and Department of Pathology, GZA Hospitals, Antwerp, Belgium. ; Royal National Orthopaedic Hospital, Middlesex, UK. UCL Cancer Institute, University College London, London, UK. ; Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK. MD Anderson Cancer Center, Houston, TX, USA. ; Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK. Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, UK. Department of Haematology, University of Cambridge, Cambridge, UK. pc8@sanger.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25082706" target="_blank"〉PubMed〈/a〉