Comprehensive molecular characterization of human colon and rectal cancer
Donna M. Muzny,Matthew N. Bainbridge,Kyle Chang,Huyen Dinh,Jennifer Drummond,Gerald R. Fowler,Christie Kovar,Lora Lewis,Margaret Morgan,Irene Newsham,Jeffrey G. Reid,Jireh Santibanez,Eve Shinbrot,Lisa R. Trevino,Yuan Qing Wu,Min Wang,Preethi H. Gunaratne,Preethi H. Gunaratne,Lawrence A. Donehower,Chad J. Creighton,David A. Wheeler,Richard A. Gibbs,Michael S. Lawrence,Douglas Voet,Rui Jing,Kristian Cibulskis,Andrey Sivachenko,Andrey Sivachenko,Petar Stojanov,Aaron McKenna,Eric S. Lander,Eric S. Lander,Stacey Gabriel,Li Ding,Robert S. Fulton,Daniel C. Koboldt,Todd Wylie,Jason Walker,David J. Dooling,Lucinda Fulton,Kim D. Delehaunty,Catrina Fronick,Ryan Demeter,Elaine R. Mardis,Richard K. Wilson,Andy Chu,Hye Jung E. Chun,Andrew J. Mungall,Erin Pleasance,A. Gordon Robertson,Dominik Stoll,Miruna Balasundaram,Inanc Birol,Yaron S.N. Butterfield,Eric Chuah,Robin J.N. Coope,Noreen Dhalla,Ranabir Guin,Carrie Hirst,Martin Hirst,Robert A. Holt,Darlene Lee,Haiyan I. Li,Michael Mayo,Richard A. Moore,Jacqueline E. Schein,Jared R. Slobodan,Angela Tam,Nina Thiessen,Richard Varhol,Thomas Zeng,Yongjun Zhao,Steven J.M. Jones,Marco A. Marra,Adam J. Bass,Alex H. Ramos,Gordon Saksena,Andrew D. Cherniack,Stephen E. Schumacher,Barbara Tabak,Scott L. Carter,Nam Pho,Huy V. Nguyen,Robert C. Onofrio,Andrew Crenshaw,Kristin G. Ardlie,Rameen Beroukhim,Wendy Winckler,Matthew Meyerson,Alexei Protopopov,Angela Hadjipanayis,Eunjung Lee,Ruibin Xi,Lixing Yang,Xiaojia Ren,Narayanan Sathiamoorthy,Peng Chieh Chen,Psalm Haseley,Yonghong Xiao,Semin Lee,Jonathan G. Seidman,Lynda Chin,Peter J. Park,Raju Kucherlapati,J. Todd Auman,Katherine A. Hoadley,Ying Du,Matthew D. Wilkerson,Yan Shi,Christina Liquori,Shaowu Meng,Ling Li,Yidi J. Turman,Michael D. Topal,Donghui Tan,Scot Waring,Elizabeth Buda,Jesse Walsh,Corbin D. Jones,Piotr A. Mieczkowski,Darshan Singh,Junyuan Wu,Anisha Gulabani,Peter Dolina,Tom Bodenheimer,Alan P. Hoyle,Janae V. Simons,Matthew G. Soloway,Lisle E. Mose,Stuart R. Jefferys,Saianand Balu,Brian O'Connor,Jan F. Prins,Derek Y. Chiang,D. Neil Hayes,Charles M. Perou,Toshinori Hinoue,Daniel J. Weisenberger,Dennis T. Maglinte,Fei Pan,Benjamin P. Berman,David Van Den Berg,Hui Shen,Timothy J. Triche,Stephen B. Baylin,Peter W. Laird,Gad Getz,Michael S. Noble,Doug Voat,Nils Gehlenborg,Daniel DiCara,Juinhua Zhang,Hailei Zhang,Chang-Jiun Wu,Spring Yingchun Liu,Sachet A. Shukla,Lihua Zhou,Pei Lin,Richard W. Park,Marc Danie Nazaire,James A. Robinson,Helga Thorvaldsdottir,Jill P. Mesirov,Vesteinn Thorsson,Sheila Reynolds,Brady Bernard,Richard Kreisberg,Jake Lin,Lisa Iype,Ryan Bressler,Timo Erkkilä,Madhumati Gundapuneni,Yuexin Liu,Adam Norberg,Thomas Robinson,Da Yang,Wei Zhang,Ilya Shmulevich,Jorma J. de Ronde,Jorma J. de Ronde,Nikolaus Schultz,Ethan Cerami,Giovanni Ciriello,Arthur P. Goldberg,Benjamin Gross,Anders Jacobsen,Jianjiong Gao,Bogumil Kaczkowski,Rileen Sinha,B. Arman Aksoy,Yevgeniy Antipin,Boris Reva,Ronglai Shen,Barry S. Taylor,Marc Ladanyi,Chris Sander,Rehan Akbani,Nianxiang Zhang,Bradley M. Broom,Tod D. Casasent,Anna K. Unruh,Chris Wakefield,Stanley R. Hamilton,R. Craig Cason,Keith A. Baggerly,John N. Weinstein,David Haussler,Christopher C. Benz,Joshua M. Stuart,Stephen C. Benz,J. Zachary Sanborn,Charles J. Vaske,Jingchun Zhu,Christopher Szeto,Gary K. Scott,Christina Yau,Sam Ng,Theodore C. Goldstein,Kyle Ellrott,Eric A. Collisson,Aaron E. Cozen,Daniel R. Zerbino,Christopher Wilks,Brian Craft,Paul T. Spellman,Robert Penny,Troy Shelton,Martha Hatfield,Scott Morris,Peggy Yena,Candace Shelton,Mark Sherman,Joseph Paulauskis,Julie M. Gastier-Foster,Julie M. Gastier-Foster,Jay Bowen,Nilsa C. Ramirez,Nilsa C. Ramirez,Aaron D. Black,Robert E. Pyatt,Robert E. Pyatt,Lisa Wise,Peter White,Peter White,Monica M. Bertagnolli,Jen Brown,Timothy A. Chan,Gerald C. Chu,Christine Czerwinski,Fred Denstman,Rajiv Dhir,Arnulf Dörner,Charles S. Fuchs,Jose G. Guillem,Mary Iacocca,Hartmut Juhl,Andrew Kaufman,Bernard Kohl,Xuan Van Le,Maria C. Mariano,Elizabeth N. Medina,Michael Meyers,Garrett M. Nash,P. Paty,Nicholas J. Petrelli,Brenda Rabeno,William G. Richards,David B. Solit,Pat Swanson,Larissa K. Temple,Joel E. Tepper,Richard Thorp,Efsevia Vakiani,Martin R. Weiser,Joseph Willis,Gary Witkin,Zhaoshi Zeng,Michael J. Zinner,Carsten Zornig,Mark A. Jensen,Robert Sfeir,Ari B. Kahn,Anna L. Chu,Prachi Kothiyal,Zhining Wang,Eric E. Snyder,Joan Pontius,Todd Pihl,Brenda Ayala,Mark Backus,Jessica Walton,Jon Whitmore,Julien Baboud,Dominique L. Berton,Matthew C. Nicholls,Deepak Srinivasan,Rohini Raman,Stanley Girshik,Peter A. Kigonya,Shelley Alonso,Rashmi N. Sanbhadti,Sean P. Barletta,John M. Greene,David Pot,Kenna R. Mills Shaw,Laura A.L. Dillon,Kenneth H. Buetow,Tanja Davidsen,John A. Demchok,Greg Eley,Martin L. Ferguson,Peter Fielding,Carl F. Schaefer,Margi Sheth,Liming Yang,Mark S. Guyer,Bradley A. Ozenberger,Jacqueline D. Palchik,Jane Peterson,Heidi J. Sofia,Elizabeth J. Thomson +320 more
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TLDR
Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression.Abstract:
To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase e (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression.read more
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The CD155/TIGIT axis promotes and maintains immune evasion in neoantigen-expressing pancreatic cancer.
William A. Freed-Pastor,William A. Freed-Pastor,Laurens J. Lambert,Zackery A. Ely,Nimisha B. Pattada,Arjun Bhutkar,George Eng,George Eng,Kim L. Mercer,Ana P. Garcia,Lin Lin,William M. Rideout,William L. Hwang,William L. Hwang,William L. Hwang,Jason M. Schenkel,Jason M. Schenkel,Alex M. Jaeger,Roderick T. Bronson,Peter M. K. Westcott,Tyler Hether,Prajan Divakar,Jason Reeves,Vikram Deshpande,Toni Delorey,Devan Phillips,Ömer H. Yilmaz,Ömer H. Yilmaz,Aviv Regev,Aviv Regev,Tyler Jacks +30 more
TL;DR: In this article, a combination immunotherapy (TIGIT/PD-1 co-blockade plus CD40 agonism) was proposed to combat this disease in preclinical models, now poised for clinical evaluation.
Journal ArticleDOI
IGF2 signaling and regulation in cancer
TL;DR: The mechanisms of IGF2 signaling and regulation in normal and malignant tissues and their clinical implications are described.
Journal ArticleDOI
E‐cadherin can limit the transforming properties of activating β‐catenin mutations
David J. Huels,Rachel A. Ridgway,Sorina Radulescu,Marc Leushacke,Andrew D. Campbell,Sujata Biswas,Sujata Biswas,Sujata Biswas,Simon J. Leedham,Simon J. Leedham,Simon J. Leedham,Stefano Serra,Runjan Chetty,Guenievre Moreaux,Lee Parry,James Matthews,Fei Song,Ann Hedley,Gabriela Kalna,Fatih Ceteci,Karen Ruth Reed,Valerie Meniel,Aoife Maguire,Brendan Doyle,Ola Söderberg,Nick Barker,Alastair J.M. Watson,Lionel Larue,Alan Richard Clarke,Owen J. Sansom +29 more
TL;DR: There is a threshold of β‐catenin that is required to drive transformation, and E‐cadherin can act as a buffer to sequester mutated β‐ catenin.
Journal ArticleDOI
Mitophagy in Intestinal Epithelial Cells Triggers Adaptive Immunity during Tumorigenesis
Paul K. Ziegler,Julia Bollrath,Charles K. Pallangyo,Takaji Matsutani,Özge Canli,Tiago De Oliveira,Michaela A. Diamanti,Nina Müller,Jaba Gamrekelashvili,Tracy L Putoczki,David Horst,Arun K. Mankan,Meryem Gülfem Öner,Susanna Müller,Josef Müller-Höcker,Thomas Kirchner,Thomas Kirchner,Julia Slotta-Huspenina,Makoto Mark Taketo,Thomas Reinheckel,Thomas Reinheckel,Stefan Dröse,Andrew C. Larner,Winfried S. Wels,Winfried S. Wels,Matthias Ernst,Tim F. Greten,Melek C. Arkan,Melek C. Arkan,Thomas Korn,Dagmar Wirth,Florian R. Greten,Florian R. Greten +32 more
TL;DR: This work unravels a complex intracellular process in intestinal epithelial cells (IECs) that controls the induction of a CD8+ T cell based adaptive immune response and highlights a so-far-unrecognized link between mitochondrial function, lysosomal integrity, and MHC class I presentation in IECs.
Journal ArticleDOI
Genetic and epigenetic alterations of colorectal cancer.
TL;DR: Molecular subtypes of CRC will permit the implementation of precision medicine with better outcome of management for CRC and molecular classification of CRC subtype based on genetic or epigenetic biomarkers for treatment response and prognosis is summarized.
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