Xin Lu1, Roman K Thomas, Martin Peifer. 1. Department of Translational Genomics, Department of Pathology and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
Abstract
MOTIVATION: Cancer genomes are characterized by the accumulation of point mutations and structural alterations such as copy-number alterations and genomic rearrangements. Among structural changes, systematic analyses of copy-number alterations have provided deeper insight into the architecture of cancer genomes and had led to new potential treatment opportunities. During the course of cancer genome evolution, selection mechanisms are leading to a non-random pattern of mutational events contributing to fitness benefits of the cancer cells. We therefore developed a new method to dissect random from non-random patterns in copy-number data and thereby to assess significantly enriched somatic copy-number aberrations across a set of tumor specimens or cell lines. In contrast to existing approaches, the method is invariant to any strictly monotonous transformation of the input data which results to an insensitivity of differences in tumor purity, array saturation effects and copy-number baseline levels. RESULTS: We applied our approach to recently published datasets of small-cell lung cancer and squamous cell lung cancer and validated its performance by comparing the results to an orthogonal approach. In addition, we found a new deletion peak containing the HLA-A gene in squamous cell lung cancer.
MOTIVATION:Cancer genomes are characterized by the accumulation of point mutations and structural alterations such as copy-number alterations and genomic rearrangements. Among structural changes, systematic analyses of copy-number alterations have provided deeper insight into the architecture of cancer genomes and had led to new potential treatment opportunities. During the course of cancer genome evolution, selection mechanisms are leading to a non-random pattern of mutational events contributing to fitness benefits of the cancer cells. We therefore developed a new method to dissect random from non-random patterns in copy-number data and thereby to assess significantly enriched somatic copy-number aberrations across a set of tumor specimens or cell lines. In contrast to existing approaches, the method is invariant to any strictly monotonous transformation of the input data which results to an insensitivity of differences in tumor purity, array saturation effects and copy-number baseline levels. RESULTS: We applied our approach to recently published datasets of small-cell lung cancer and squamous cell lung cancer and validated its performance by comparing the results to an orthogonal approach. In addition, we found a new deletion peak containing the HLA-A gene in squamous cell lung cancer.
Authors: Julie George; Jing Shan Lim; Se Jin Jang; Yupeng Cun; Luka Ozretić; Gu Kong; Frauke Leenders; Xin Lu; Lynnette Fernández-Cuesta; Graziella Bosco; Christian Müller; Ilona Dahmen; Nadine S Jahchan; Kwon-Sik Park; Dian Yang; Anthony N Karnezis; Dedeepya Vaka; Angela Torres; Maia Segura Wang; Jan O Korbel; Roopika Menon; Sung-Min Chun; Deokhoon Kim; Matt Wilkerson; Neil Hayes; David Engelmann; Brigitte Pützer; Marc Bos; Sebastian Michels; Ignacija Vlasic; Danila Seidel; Berit Pinther; Philipp Schaub; Christian Becker; Janine Altmüller; Jun Yokota; Takashi Kohno; Reika Iwakawa; Koji Tsuta; Masayuki Noguchi; Thomas Muley; Hans Hoffmann; Philipp A Schnabel; Iver Petersen; Yuan Chen; Alex Soltermann; Verena Tischler; Chang-min Choi; Yong-Hee Kim; Pierre P Massion; Yong Zou; Dragana Jovanovic; Milica Kontic; Gavin M Wright; Prudence A Russell; Benjamin Solomon; Ina Koch; Michael Lindner; Lucia A Muscarella; Annamaria la Torre; John K Field; Marko Jakopovic; Jelena Knezevic; Esmeralda Castaños-Vélez; Luca Roz; Ugo Pastorino; Odd-Terje Brustugun; Marius Lund-Iversen; Erik Thunnissen; Jens Köhler; Martin Schuler; Johan Botling; Martin Sandelin; Montserrat Sanchez-Cespedes; Helga B Salvesen; Viktor Achter; Ulrich Lang; Magdalena Bogus; Peter M Schneider; Thomas Zander; Sascha Ansén; Michael Hallek; Jürgen Wolf; Martin Vingron; Yasushi Yatabe; William D Travis; Peter Nürnberg; Christian Reinhardt; Sven Perner; Lukas Heukamp; Reinhard Büttner; Stefan A Haas; Elisabeth Brambilla; Martin Peifer; Julien Sage; Roman K Thomas Journal: Nature Date: 2015-07-13 Impact factor: 49.962
Authors: Julie George; Vonn Walter; Martin Peifer; Ludmil B Alexandrov; Danila Seidel; Frauke Leenders; Lukas Maas; Christian Müller; Ilona Dahmen; Tiffany M Delhomme; Maude Ardin; Noemie Leblay; Graham Byrnes; Ruping Sun; Aurélien De Reynies; Anne McLeer-Florin; Graziella Bosco; Florian Malchers; Roopika Menon; Janine Altmüller; Christian Becker; Peter Nürnberg; Viktor Achter; Ulrich Lang; Peter M Schneider; Magdalena Bogus; Matthew G Soloway; Matthew D Wilkerson; Yupeng Cun; James D McKay; Denis Moro-Sibilot; Christian G Brambilla; Sylvie Lantuejoul; Nicolas Lemaitre; Alex Soltermann; Walter Weder; Verena Tischler; Odd Terje Brustugun; Marius Lund-Iversen; Åslaug Helland; Steinar Solberg; Sascha Ansén; Gavin Wright; Benjamin Solomon; Luca Roz; Ugo Pastorino; Iver Petersen; Joachim H Clement; Jörg Sänger; Jürgen Wolf; Martin Vingron; Thomas Zander; Sven Perner; William D Travis; Stefan A Haas; Magali Olivier; Matthieu Foll; Reinhard Büttner; David Neil Hayes; Elisabeth Brambilla; Lynnette Fernandez-Cuesta; Roman K Thomas Journal: Nat Commun Date: 2018-03-13 Impact factor: 14.919