Current Clinical Pathology Antonio Giordano, Md, Phd SERIES EDITOR For further volumes: http://www.springer.com/series/7632 Antonio Russo ● Stefano Iacobelli ● Juan Iovanna Editors Diagnostic, Prognostic and Therapeutic Value of Gene Signatures Editors Antonio Russo, MD, PhD Stefano Iacobelli, MD Section of Medical Oncology National Consortium for Research on Cancer (CINBO) Department of Surgical and Oncological Sciences University D’Annunzio University of Palermo Chieti 66013, Italy Palermo, Italy [email protected] [email protected] Juan Iovanna, MD, PhD INSERM U624 Marseille 13288, France [email protected] ISBN 978-1-61779-357-8 e-ISBN 978-1-61779-358-5 DOI 10.1007/978-1-61779-358-5 Springer New York Dordrecht Heidelberg London Library of Congress Control Number: 2011937026 © Springer Science+Business Media, LLC 2012 All rights reserved. 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The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Humana Press is part of Springer Science+Business Media (www.springer.com) Preface Gene expression studies have revealed diagnostic profiles and upregulation of specific pathways in many solid tumors. Some gene-expression signatures are already used as predictors of relapse in early breast cancer patients. The explosion of new information in gene expression profiling could potentially lead to the development of tailored treatments in many solid tumors. In addition, many studies are ongoing to validate these signatures also in predicting response to hormonal, chemo- therapeutic, and targeted agents in breast cancer as well as in other tumors. This book has been carried out with the aim of providing readers a useful and comprehensive resource about the range of applications of microarray technology on oncological diseases. The book is principally addressed to resident and fellow physicians, medical oncologists, molec- ular biologists, biotechnologists, and those who study oncological diseases. The chapters have been written by leading international researchers on these topics who have prepared their manuscripts according to current literature and field experience with microarray technology. Palermo, Italy Antonio Russo Chieti, Italy Stefano Iacobelli Marseille, France Juan Iovanna v Contents 1 Gene Signatures and Soft Tissue Sarcomas: Status of Art and Perspectives ..................................................................................................... 1 Bruno Vincenzi, Anna Maria Frezza, Daniele Santini, and Giuseppe Tonini 2 Heterogeneity of Breast Cancer: Gene Signatures and Beyond ................................... 13 Gaia Schiavon, Marcel Smid, Gaorav P. Gupta, Stefania Redana, Daniele Santini, and John W.M. Martens 3 Gene Signatures in CRC and Liver Metastasis .............................................................. 27 Daniele Fanale, Lidia Corsini, Sergio Rizzo, and Antonio Russo 4 Gene Signatures in Gastrointestinal Stromal Tumors ................................................... 35 Piotr Rutkowski, Giuseppe Badalamenti, Laura La Paglia, Joanna Przybył, and Maria Debiec-Rychter 5 Pancreatic Cancer Genetics ............................................................................................. 51 Juan Iovanna, Ezequiel Luis Calvo, Jean Charles Dagorn, and Nelson Dusetti 6 Diagnostic, Prognostic, and Therapeutic Value of Gene Signatures in Non-Small Cell Lung Cancer....................................................................................... 81 Rafael Rosell, Miquel Taron, Christian Diego Rolfo, Delvys Rodriguez-Abreu, and Jia Wei 7 Gene Signatures in Gastric Cancer ................................................................................. 95 Laura Ottini, Mario Falchetti, and Gabriella Nesi 8 Gene Signatures in Colorectal Cancer ............................................................................ 115 Alessandro Lugli and Inti Zlobec 9 The Role of Epigenetics in Cancer: From Molecular Function to High-Throughput Assays ............................................................................................. 137 Aleksandra Pekowska, Joaquin Zacarias-Cabeza, Jinsong Jia, Pierre Ferrier, and Salvatore Spicuglia vii viii Contents 10 Primary Epithelial Ovarian Neoplasms: New Concepts Concerning Origin, Pathogenesis and Classifi cation Based on Morphology, Immunomarkers, Molecular Features, and Gene Expression Studies ........................................................................................... 153 Bernard Czernobilsky, Leonor Leider-Trejo, Daniele Fanale, and Antonio Russo 11 Thyroid Carcinoma: Molecular Signature by Histotype-Specifi c Mutations and Gene Expression Patterns ...................................................................... 165 Umberto Malapelle, Claudio Bellevicine, Lajos Pustzai, and Giancarlo Troncone Index ........................................................................................................................................... 179 Contributors Giuseppe Badalamenti , MD, PhD Section of Medical Oncology , Department of Surgical and Oncological Sciences, University of Palermo , Palermo , Italy Claudio Bellevicine , MD Scienze Biomorfologiche e Funzionali , Universita degli Studi di Napoli Federico II , Naples , Italy Ezequiel Luis Calvo , MD, PhD Centre de Recherche du CHUL (CHUQ) , Quebec , PQ , Canada Lidia Corsini , PhD Section of Medical Oncology, Department of Surgical and Oncological Sciences , University of Palermo , Palermo , Italy Bernard Czernobilsky , MD Patho-Lab Diagnostics , Ness Ziona , Israel Jean Charles Dagorn , PhD INSERM U624 , Marseille , France Maria Debiec-Rychter , MD, PhD Department of Human Genetics , Catholic University of Leuven , Leuven , Belgium Nelson Dusetti , PhD INSERM U624 , Marseille , France Mario Falchetti , PhD Department of Molecular Medicine, Policlinico Umberto I, Sapienza University of Rome , Rome , Italy Daniele Fanale , PhD Section of Medical Oncology, Department of Surgical and Oncological Sciences , University of Palermo , Palermo , Italy Pierre Ferrier , PhD Centre d’Immunologie de Marseille-Luminy, Université Aix-Marseille, France CNRS, UMR6102, Marseille, France Inserm, U631, Marseille, France Anna Maria Frezza , MD Department of Medical Oncology , University Campus Bio-Medico , Rome , Italy Gaorav P. Gupta , MD, PhD Department of Radiation Oncology , Memorial Sloan-Kettering Cancer Center , New York , NY , USA Stefano Iacobelli , MD National Consortium for Research on Cancer (CINBO), University D’Annunzio , Chieti , Italy Juan Iovanna , MD, PhD INSERM U624 , Marseille , France ix x Contributors Jinsong Jia , MD, PhD Centre d’Immunologie de Marseille-Luminy, Université Aix-Marseille , France CNRS, UMR6102, Marseille, France Inserm, U631, Marseille, France Institute of Hematology, People’s Hospital, Beijing University, Beijing, People’s Republic of China Laura La Paglia , PhD Section of Medical Oncology, Department of Surgical and Oncological Sciences , University of Palermo , Palermo , Italy Leonor Leider-Trejo , MD Institute of Pathology, Sourasky Medical Center , Tel Aviv , Israel Alessandro Lugli , MD Institute of Pathology, University of Bern , Bern , Switzerland Umberto Malapelle , MD, BS Scienze Biomorfologiche e Funzionali , Universita degli Studi di Napoli Federico II , Naples , Italy John W. M. Martens , PhD Department of Medical Oncology , Daniel den Hoed Cancer Center, Erasmus Medical Center , Rotterdam , The Netherlands Gabriella Nesi , MD, PhD Department of Critical Care Medicine, Division of Pathological Anatomy, University of Florence , Florence , Italy Laura Ottini , MD, PhD Department of Molecular Medicine , Policlinico Umberto I, Sapienza University of Rome , Rome , Italy Aleksandra Pekowska , PhD Centre d’Immunologie de Marseille-Luminy, Université Aix-Marseille, France CNRS, UMR6102, Marseille, France Inserm, U631, Marseille, France Joanna Przybył , MSc Department of Molecular Biology , Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology , Warsaw , Poland Lajos Pustzai , MD, DPhil Department of Breast Medical Oncology , MD Anderson Cancer Center, University of Texas , Houston , TX , USA Stefania Redana , MD Department of Medical Oncology I , Institute for Cancer Research and Treatment, Fondazione Piemontese per L’Oncologia , Candiolo , Italy Sergio Rizzo , MD, PhD Section of Medical Oncology, Department of Surgical and Oncological Sciences , University of Palermo , Palermo , Italy Delvys Rodriguez-Abreu , MD Department of Medical Oncology , Universitario Insular de Gran Canaria , Las Palmas de