Background & Aims
Methods
Results
Conclusions
Graphical abstract

Keywords
Abbreviations used in this paper:
ATCC (American Type Culture Collection), BE (Barrett’s esophagus), EAC (esophageal adenocarcinoma), ERBB2 (erb-b2 receptor tyrosine kinase 2), ESCC (esophageal squamous cell carcinoma), FCS (fetal calf serum), GEM (gene expression microarray), GERD (gastroesophageal reflux disease), GO (gene ontology), HGD (high-grade dysplastic), IL (interleukin), LIF (leukemia inhibitory factor), JAK-STAT (Janus kinase/signal transducer-and-activator of transcription), mRNA (messenger RNA), MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), PBS (phosphate-buffered saline), RA (rheumatoid arthritis), siRNA (small interfering RNA), SV (somatic variation), SYK (spleen tyrosine kinase), TCGA (The Cancer Genome Atlas), TREM2 (triggering receptor expressed on myeloid cells 2), VEGFA (vascular endothelial growth factor A)- Agrawal N.
- Jiao Y.
- Bettegowda C.
- Hutfless S.M.
- Wang Y.
- David S.
- Cheng Y.
- Twaddell W.S.
- Latt N.L.
- Shin E.J.
- Wang L.D.
- Wang L.
- Yang W.
- Velculescu V.E.
- Vogelstein B.
- Papadopoulos N.
- Kinzler K.W.
- Meltzer S.J.
- Kandioler D.
- Schoppmann S.F.
- Zwrtek R.
- Kappel S.
- Wolf B.
- Mittlbock M.
- Kuhrer I.
- Hejna M.
- Pluschnig U.
- Ba-Ssalamah A.
- Wrba F.
- Zacherl J.
- Yamamoto Y.
- Wang X.
- Bertrand D.
- Kern F.
- Zhang T.
- Duleba M.
- Srivastava S.
- Khor C.C.
- Hu Y.
- Wilson L.H.
- Blaszyk H.
- Rolshud D.
- Teh M.
- Liu J.
- Howitt B.E.
- Vincent M.
- Crum C.P.
- Nagarajan N.
- Ho K.Y.
- McKeon F.
- Xian W.
- Chong I.Y.
- Cunningham D.
- Barber L.J.
- Campbell J.
- Chen L.
- Kozarewa I.
- Fenwick K.
- Assiotis I.
- Guettler S.
- Garcia-Murillas I.
- Awan S.
- Lambros M.
- Starling N.
- Wotherspoon A.
- Stamp G.
- Gonzalez-de-Castro D.
- Benson M.
- Chau I.
- Hulkki S.
- Nohadani M.
- Eltahir Z.
- Lemnrau A.
- Orr N.
- Rao S.
- Lord C.J.
- Ashworth A.
- Dulak A.M.
- Stojanov P.
- Peng S.
- Lawrence M.S.
- Fox C.
- Stewart C.
- Bandla S.
- Imamura Y.
- Schumacher S.E.
- Shefler E.
- McKenna A.
- Carter S.L.
- Cibulskis K.
- Sivachenko A.
- Saksena G.
- Voet D.
- Ramos A.H.
- Auclair D.
- Thompson K.
- Sougnez C.
- Onofrio R.C.
- Guiducci C.
- Beroukhim R.
- Zhou Z.
- Lin L.
- Lin J.
- Reddy R.
- Chang A.
- Landrenau R.
- Pennathur A.
- Ogino S.
- Luketich J.D.
- Golub T.R.
- Gabriel S.B.
- Lander E.S.
- Beer D.G.
- Godfrey T.E.
- Getz G.
- Bass A.J.
- Streppel M.M.
- Lata S.
- DelaBastide M.
- Montgomery E.A.
- Wang J.S.
- Canto M.I.
- Macgregor-Das A.M.
- Pai S.
- Morsink F.H.
- Offerhaus G.J.
- Antoniou E.
- Maitra A.
- McCombie W.R.
Integrated genomic characterization of oesophageal carcinoma.
- Agrawal N.
- Jiao Y.
- Bettegowda C.
- Hutfless S.M.
- Wang Y.
- David S.
- Cheng Y.
- Twaddell W.S.
- Latt N.L.
- Shin E.J.
- Wang L.D.
- Wang L.
- Yang W.
- Velculescu V.E.
- Vogelstein B.
- Papadopoulos N.
- Kinzler K.W.
- Meltzer S.J.
- Weaver J.M.
- Ross-Innes C.S.
- Shannon N.
- Lynch A.G.
- Forshew T.
- Barbera M.
- Murtaza M.
- Ong C.A.
- Lao-Sirieix P.
- Dunning M.J.
- Smith L.
- Smith M.L.
- Anderson C.L.
- Carvalho B.
- O'Donovan M.
- Underwood T.J.
- May A.P.
- Grehan N.
- Hardwick R.
- Davies J.
- Oloumi A.
- Aparicio S.
- Caldas C.
- Eldridge M.D.
- Edwards P.A.
- Rosenfeld N.
- Tavare S.
- Fitzgerald R.C.
Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis.
- Secrier M.
- Li X.
- de Silva N.
- Eldridge M.D.
- Contino G.
- Bornschein J.
- MacRae S.
- Grehan N.
- O'Donovan M.
- Miremadi A.
- Yang T.P.
- Bower L.
- Chettouh H.
- Crawte J.
- Galeano-Dalmau N.
- Grabowska A.
- Saunders J.
- Underwood T.
- Waddell N.
- Barbour A.P.
- Nutzinger B.
- Achilleos A.
- Edwards P.A.
- Lynch A.G.
- Tavare S.
- Fitzgerald R.C.
Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance.
- Kim J.
- Fox C.
- Peng S.
- Pusung M.
- Pectasides E.
- Matthee E.
- Hong Y.S.
- Do I.G.
- Jang J.
- Thorner A.R.
- Van Hummelen P.
- Rustgi A.K.
- Wong K.K.
- Zhou Z.
- Tang P.
- Kim K.M.
- Lee J.
- Bass A.J.
- Duggan S.P.
- Behan F.M.
- Kirca M.
- Smith S.
- Reynolds J.V.
- Long A.
- Kelleher D.
Materials and Methods
Cell Lines and Cell Culture
Clinical Tissue Collection, RNA Extraction, and Immunohistochemistry
- Duggan S.P.
- Behan F.M.
- Kirca M.
- Zaheer A.
- McGarrigle S.A.
- Reynolds J.V.
- Vaz G.M.
- Senge M.O.
- Kelleher D.
Small Interfering RNA–Mediated Silencing
High-Throughput siRNA Library Screening
Protein Expression Analysis
- Duggan S.P.
- Behan F.M.
- Kirca M.
- Smith S.
- Reynolds J.V.
- Long A.
- Kelleher D.
- Duggan S.P.
- Behan F.M.
- Kirca M.
- Zaheer A.
- McGarrigle S.A.
- Reynolds J.V.
- Vaz G.M.
- Senge M.O.
- Kelleher D.
Gene Expression Microarray Re-analysis and Bioinformatics
- Kimchi E.T.
- Posner M.C.
- Park J.O.
- Darga T.E.
- Kocherginsky M.
- Karrison T.
- Hart J.
- Smith K.D.
- Mezhir J.J.
- Weichselbaum R.R.
- Khodarev N.N.
- Duggan S.P.
- Behan F.M.
- Kirca M.
- Zaheer A.
- McGarrigle S.A.
- Reynolds J.V.
- Vaz G.M.
- Senge M.O.
- Kelleher D.
Cellular Assays of Viability, Apoptosis, and Gene Expression
Gene Expression Analysis
- Duggan S.P.
- Behan F.M.
- Kirca M.
- Smith S.
- Reynolds J.V.
- Long A.
- Kelleher D.
- Duggan S.P.
- Behan F.M.
- Kirca M.
- Zaheer A.
- McGarrigle S.A.
- Reynolds J.V.
- Vaz G.M.
- Senge M.O.
- Kelleher D.
Murine Subcutaneous Xenografts
Statistical Analysis
- Duggan S.P.
- Behan F.M.
- Kirca M.
- Smith S.
- Reynolds J.V.
- Long A.
- Kelleher D.
- Duggan S.P.
- Behan F.M.
- Kirca M.
- Zaheer A.
- McGarrigle S.A.
- Reynolds J.V.
- Vaz G.M.
- Senge M.O.
- Kelleher D.
Results
Druggable Genome Screening of EAC Cell Growth After siRNA-Mediated Silencing
- Duggan S.P.
- Behan F.M.
- Kirca M.
- Zaheer A.
- McGarrigle S.A.
- Reynolds J.V.
- Vaz G.M.
- Senge M.O.
- Kelleher D.

Somatic Gene Amplifications Associate With Druggable Genome siRNA-Targeted Genes
Integrated genomic characterization of oesophageal carcinoma.
- Su Z.
- Gay L.J.
- Strange A.
- Palles C.
- Band G.
- Whiteman D.C.
- Lescai F.
- Langford C.
- Nanji M.
- Edkins S.
- van der Winkel A.
- Levine D.
- Sasieni P.
- Bellenguez C.
- Howarth K.
- Freeman C.
- Trudgill N.
- Tucker A.T.
- Pirinen M.
- Peppelenbosch M.P.
- van der Laan L.J.W.
- Kuipers E.J.
- Drenth J.P.H.
- Peters W.H.
- Reynolds J.V.
- Kelleher D.P.
- McManus R.
- Grabsch H.
- Prenen H.
- Bisschops R.
- Krishnadath K.
- Siersema P.D.
- van Baal J.W.P.M.
- Middleton M.
- Petty R.
- Gillies R.
- Burch N.
- Bhandari P.
- Paterson S.
- Edwards C.
- Penman I.
- Vaidya K.
- Ang Y.
- Murray I.
- Patel P.
- Ye W.
- Mullins P.
- Wu A.H.
- Bird N.C.
- Dallal H.
- Shaheen N.J.
- Murray L.J.
- Koss K.
- Bernstein L.
- Romero Y.
- Hardie L.J.
- Zhang R.
- Winter H.
- Corley D.A.
- Panter S.
- Risch H.A.
- Reid B.J.
- Sargeant I.
- Gammon M.D.
- Smart H.
- Dhar A.
- McMurtry H.
- Ali H.
- Liu G.
- Casson A.G.
- Chow W.-H.
- Rutter M.
- Tawil A.
- Morris D.
- Nwokolo C.
- Isaacs P.
- Rodgers C.
- Ragunath K.
- MacDonald C.
- Haigh C.
- Monk D.
- Davies G.
- Wajed S.
- Johnston D.
- Gibbons M.
- Cullen S.
- Church N.
- Langley R.
- Griffin M.
- Alderson D.
- Deloukas P.
- Hunt S.E.
- Gray E.
- Dronov S.
- Potter S.C.
- Tashakkori-Ghanbaria A.
- Anderson M.
- Brooks C.
- Blackwell J.M.
- Bramon E.
- Brown M.A.
- Casas J.P.
- Corvin A.
- Duncanson A.
- Markus H.S.
- Mathew C.G.
- Palmer C.N.A.
- Plomin R.
- Rautanen A.
- Sawcer S.J.
- Trembath R.C.
- Viswanathan A.C.
- Wood N.
- Trynka G.
- Wijmenga C.
- Cazier J.-B.
- Atherfold P.
- Nicholson A.M.
- Gellatly N.L.
- Glancy D.
- Cooper S.C.
- Cunningham D.
- Lind T.
- Hapeshi J.
- Ferry D.
- Rathbone B.
- Brown J.
- Love S.
- Attwood S.
- MacGregor S.
- Watson P.
- Sanders S.
- Ek W.
- Harrison R.F.
- Moayyedi P.
- de Caestecker J.
- Barr H.
- Stupka E.
- Vaughan T.L.
- Peltonen L.
- Spencer C.C.A.
- Tomlinson I.
- Donnelly P.
- Jankowski J.A.Z.
- Gharahkhani P.
- Fitzgerald R.C.
- Vaughan T.L.
- Palles C.
- Gockel I.
- Tomlinson I.
- Buas M.F.
- May A.
- Gerges C.
- Anders M.
- Becker J.
- Kreuser N.
- Noder T.
- Venerito M.
- Veits L.
- Schmidt T.
- Manner H.
- Schmidt C.
- Hess T.
- Böhmer A.C.
- Izbicki J.R.
- Hölscher A.H.
- Lang H.
- Lorenz D.
- Schumacher B.
- Hackelsberger A.
- Mayershofer R.
- Pech O.
- Vashist Y.
- Ott K.
- Vieth M.
- Weismüller J.
- Nöthen M.M.
- Attwood S.
- Barr H.
- Chegwidden L.
- de Caestecker J.
- Harrison R.
- Love S.B.
- MacDonald D.
- Moayyedi P.
- Prenen H.
- Watson R.G.P.
- Iyer P.G.
- Anderson L.A.
- Bernstein L.
- Chow W.H.
- Hardie L.J.
- Lagergren J.
- Liu G.
- Risch H.A.
- Wu A.H.
- Ye W.
- Bird N.C.
- Shaheen N.J.
- Gammon M.D.
- Corley D.A.
- Caldas C.
- Moebus S.
- Knapp M.
- Peters W.H.M.
- Neuhaus H.
- Rösch T.
- Ell C.
- MacGregor S.
- Pharoah P.
- Whiteman D.C.
- Jankowski J.
- Schumacher J.
Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis.

Innate-Immune Lymphoid Factors Are Enriched Gene Ontologies Supporting EAC Cell Growth
- Pribluda A.
- Elyada E.
- Wiener Z.
- Hamza H.
- Goldstein R.E.
- Biton M.
- Burstain I.
- Morgenstern Y.
- Brachya G.
- Billauer H.
- Biton S.
- Snir-Alkalay I.
- Vucic D.
- Schlereth K.
- Mernberger M.
- Stiewe T.
- Oren M.
- Alitalo K.
- Pikarsky E.
- Ben-Neriah Y.

Overexpression of LIF, C1QA, and TREM2 in the BE-Associated Cancer Sequence
- Duggan S.P.
- Behan F.M.
- Kirca M.
- Zaheer A.
- McGarrigle S.A.
- Reynolds J.V.
- Vaz G.M.
- Senge M.O.
- Kelleher D.

- Duggan S.P.
- Behan F.M.
- Kirca M.
- Zaheer A.
- McGarrigle S.A.
- Reynolds J.V.
- Vaz G.M.
- Senge M.O.
- Kelleher D.

LIF Maintains EAC Cell Survival, Constitutive Levels of phospho-STAT3, IL6, and C1QA
- Duggan S.P.
- Behan F.M.
- Kirca M.
- Smith S.
- Reynolds J.V.
- Long A.
- Kelleher D.
- Quante M.
- Bhagat G.
- Abrams J.A.
- Marache F.
- Good P.
- Lee M.D.
- Lee Y.
- Friedman R.
- Asfaha S.
- Dubeykovskaya Z.
- Mahmood U.
- Figueiredo J.L.
- Kitajewski J.
- Shawber C.
- Lightdale C.J.
- Rustgi A.K.
- Wang T.C.
- Piccio L.
- Buonsanti C.
- Cella M.
- Tassi I.
- Schmidt R.E.
- Fenoglio C.
- Rinker 2nd, J.
- Naismith R.T.
- Panina-Bordignon P.
- Passini N.
- Galimberti D.
- Scarpini E.
- Colonna M.
- Cross A.H.

Autocrine Non–Complement-Mediated Promotion of EAC Cell Growth by C1q
- Naito A.T.
- Sumida T.
- Nomura S.
- Liu M.L.
- Higo T.
- Nakagawa A.
- Okada K.
- Sakai T.
- Hashimoto A.
- Hara Y.
- Shimizu I.
- Zhu W.
- Toko H.
- Katada A.
- Akazawa H.
- Oka T.
- Lee J.K.
- Minamino T.
- Nagai T.
- Walsh K.
- Kikuchi A.
- Matsumoto M.
- Botto M.
- Shiojima I.
- Komuro I.
- Okada K.
- Naito A.T.
- Higo T.
- Nakagawa A.
- Shibamoto M.
- Sakai T.
- Hashimoto A.
- Kuramoto Y.
- Sumida T.
- Nomura S.
- Ito M.
- Yamaguchi T.
- Oka T.
- Akazawa H.
- Lee J.K.
- Morimoto S.
- Sakata Y.
- Shiojima I.
- Komuro I.

TREM2 and Its Associated Signaling Pathway Regulates EAC Cell Survival
- Jonsson T.
- Stefansson H.
- Steinberg S.
- Jonsdottir I.
- Jonsson P.V.
- Snaedal J.
- Bjornsson S.
- Huttenlocher J.
- Levey A.I.
- Lah J.J.
- Rujescu D.
- Hampel H.
- Giegling I.
- Andreassen O.A.
- Engedal K.
- Ulstein I.
- Djurovic S.
- Ibrahim-Verbaas C.
- Hofman A.
- Ikram M.A.
- van Duijn C.M.
- Thorsteinsdottir U.
- Kong A.
- Stefansson K.
Targeting the Immune Signature of EAC Cells With Fostamatinib
- Weinblatt M.E.
- Kavanaugh A.
- Burgos-Vargas R.
- Dikranian A.H.
- Medrano-Ramirez G.
- Morales-Torres J.L.
- Murphy F.T.
- Musser T.K.
- Straniero N.
- Vicente-Gonzales A.V.
- Grossbard E.
- Flinn I.W.
- Bartlett N.L.
- Blum K.A.
- Ardeshna K.M.
- LaCasce A.S.
- Flowers C.R.
- Shustov A.R.
- Thress K.S.
- Mitchell P.
- Zheng F.
- Skolnik J.M.
- Friedberg J.W.

Discussion
- Pribluda A.
- Elyada E.
- Wiener Z.
- Hamza H.
- Goldstein R.E.
- Biton M.
- Burstain I.
- Morgenstern Y.
- Brachya G.
- Billauer H.
- Biton S.
- Snir-Alkalay I.
- Vucic D.
- Schlereth K.
- Mernberger M.
- Stiewe T.
- Oren M.
- Alitalo K.
- Pikarsky E.
- Ben-Neriah Y.
- Pribluda A.
- Elyada E.
- Wiener Z.
- Hamza H.
- Goldstein R.E.
- Biton M.
- Burstain I.
- Morgenstern Y.
- Brachya G.
- Billauer H.
- Biton S.
- Snir-Alkalay I.
- Vucic D.
- Schlereth K.
- Mernberger M.
- Stiewe T.
- Oren M.
- Alitalo K.
- Pikarsky E.
- Ben-Neriah Y.
- Pal J.
- Bertheau R.
- Buon L.
- Qazi A.
- Batchu R.B.
- Bandyopadhyay S.
- Ali-Fehmi R.
- Beer D.G.
- Weaver D.W.
- Shmookler Reis R.J.
- Goyal R.K.
- Huang Q.
- Munshi N.C.
- Shammas M.A.
Integrated genomic characterization of oesophageal carcinoma.
- Su Z.
- Gay L.J.
- Strange A.
- Palles C.
- Band G.
- Whiteman D.C.
- Lescai F.
- Langford C.
- Nanji M.
- Edkins S.
- van der Winkel A.
- Levine D.
- Sasieni P.
- Bellenguez C.
- Howarth K.
- Freeman C.
- Trudgill N.
- Tucker A.T.
- Pirinen M.
- Peppelenbosch M.P.
- van der Laan L.J.W.
- Kuipers E.J.
- Drenth J.P.H.
- Peters W.H.
- Reynolds J.V.
- Kelleher D.P.
- McManus R.
- Grabsch H.
- Prenen H.
- Bisschops R.
- Krishnadath K.
- Siersema P.D.
- van Baal J.W.P.M.
- Middleton M.
- Petty R.
- Gillies R.
- Burch N.
- Bhandari P.
- Paterson S.
- Edwards C.
- Penman I.
- Vaidya K.
- Ang Y.
- Murray I.
- Patel P.
- Ye W.
- Mullins P.
- Wu A.H.
- Bird N.C.
- Dallal H.
- Shaheen N.J.
- Murray L.J.
- Koss K.
- Bernstein L.
- Romero Y.
- Hardie L.J.
- Zhang R.
- Winter H.
- Corley D.A.
- Panter S.
- Risch H.A.
- Reid B.J.
- Sargeant I.
- Gammon M.D.
- Smart H.
- Dhar A.
- McMurtry H.
- Ali H.
- Liu G.
- Casson A.G.
- Chow W.-H.
- Rutter M.
- Tawil A.
- Morris D.
- Nwokolo C.
- Isaacs P.
- Rodgers C.
- Ragunath K.
- MacDonald C.
- Haigh C.
- Monk D.
- Davies G.
- Wajed S.
- Johnston D.
- Gibbons M.
- Cullen S.
- Church N.
- Langley R.
- Griffin M.
- Alderson D.
- Deloukas P.
- Hunt S.E.
- Gray E.
- Dronov S.
- Potter S.C.
- Tashakkori-Ghanbaria A.
- Anderson M.
- Brooks C.
- Blackwell J.M.
- Bramon E.
- Brown M.A.
- Casas J.P.
- Corvin A.
- Duncanson A.
- Markus H.S.
- Mathew C.G.
- Palmer C.N.A.
- Plomin R.
- Rautanen A.
- Sawcer S.J.
- Trembath R.C.
- Viswanathan A.C.
- Wood N.
- Trynka G.
- Wijmenga C.
- Cazier J.-B.
- Atherfold P.
- Nicholson A.M.
- Gellatly N.L.
- Glancy D.
- Cooper S.C.
- Cunningham D.
- Lind T.
- Hapeshi J.
- Ferry D.
- Rathbone B.
- Brown J.
- Love S.
- Attwood S.
- MacGregor S.
- Watson P.
- Sanders S.
- Ek W.
- Harrison R.F.
- Moayyedi P.
- de Caestecker J.
- Barr H.
- Stupka E.
- Vaughan T.L.
- Peltonen L.
- Spencer C.C.A.
- Tomlinson I.
- Donnelly P.
- Jankowski J.A.Z.
- Gharahkhani P.
- Fitzgerald R.C.
- Vaughan T.L.
- Palles C.
- Gockel I.
- Tomlinson I.
- Buas M.F.
- May A.
- Gerges C.
- Anders M.
- Becker J.
- Kreuser N.
- Noder T.
- Venerito M.
- Veits L.
- Schmidt T.
- Manner H.
- Schmidt C.
- Hess T.
- Böhmer A.C.
- Izbicki J.R.
- Hölscher A.H.
- Lang H.
- Lorenz D.
- Schumacher B.
- Hackelsberger A.
- Mayershofer R.
- Pech O.
- Vashist Y.
- Ott K.
- Vieth M.
- Weismüller J.
- Nöthen M.M.
- Attwood S.
- Barr H.
- Chegwidden L.
- de Caestecker J.
- Harrison R.
- Love S.B.
- MacDonald D.
- Moayyedi P.
- Prenen H.
- Watson R.G.P.
- Iyer P.G.
- Anderson L.A.
- Bernstein L.
- Chow W.H.
- Hardie L.J.
- Lagergren J.
- Liu G.
- Risch H.A.
- Wu A.H.
- Ye W.
- Bird N.C.
- Shaheen N.J.
- Gammon M.D.
- Corley D.A.
- Caldas C.
- Moebus S.
- Knapp M.
- Peters W.H.M.
- Neuhaus H.
- Rösch T.
- Ell C.
- MacGregor S.
- Pharoah P.
- Whiteman D.C.
- Jankowski J.
- Schumacher J.
Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis.
- Palles C.
- Chegwidden L.
- Li X.
- Findlay J.M.
- Farnham G.
- Castro Giner F.
- Peppelenbosch M.P.
- Kovac M.
- Adams C.L.
- Prenen H.
- Briggs S.
- Harrison R.
- Sanders S.
- MacDonald D.
- Haigh C.
- Tucker A.
- Love S.
- Nanji M.
- deCaestecker J.
- Ferry D.
- Rathbone B.
- Hapeshi J.
- Barr H.
- Moayyedi P.
- Watson P.
- Zietek B.
- Maroo N.
- Gay L.
- Underwood T.
- Boulter L.
- McMurtry H.
- Monk D.
- Patel P.
- Ragunath K.
- Al Dulaimi D.
- Murray I.
- Koss K.
- Veitch A.
- Trudgill N.
- Nwokolo C.
- Rembacken B.
- Atherfold P.
- Green E.
- Ang Y.
- Kuipers E.J.
- Chow W.
- Paterson S.
- Kadri S.
- Beales I.
- Grimley C.
- Mullins P.
- Beckett C.
- Farrant M.
- Dixon A.
- Kelly S.
- Johnson M.
- Wajed S.
- Dhar A.
- Sawyer E.
- Roylance R.
- Onstad L.
- Gammon M.D.
- Corley D.A.
- Shaheen N.J.
- Bird N.C.
- Hardie L.J.
- Reid B.J.
- Ye W.
- Liu G.
- Romero Y.
- Bernstein L.
- Wu A.H.
- Casson A.G.
- Fitzgerald R.
- Whiteman D.C.
- Risch H.A.
- Levine D.M.
- Vaughan T.L.
- Verhaar A.P.
- van den Brande J.
- Toxopeus E.L.
- Spaander M.C.
- Wijnhoven B.P.
- van der Laan L.J.
- Krishnadath K.
- Wijmenga C.
- Trynka G.
- McManus R.
- Reynolds J.V.
- O'Sullivan J.
- MacMathuna P.
- McGarrigle S.A.
- Kelleher D.
- Vermeire S.
- Cleynen I.
- Bisschops R.
- Tomlinson I.
- Jankowski J.
Integrated genomic characterization of oesophageal carcinoma.
- Cunningham D.
- Stenning S.P.
- Smyth E.C.
- Okines A.F.
- Allum W.H.
- Rowley S.
- Stevenson L.
- Grabsch H.I.
- Alderson D.
- Crosby T.
- Griffin S.M.
- Mansoor W.
- Coxon F.Y.
- Falk S.J.
- Darby S.
- Sumpter K.A.
- Blazeby J.M.
- Langley R.E.
- Alonso R.
- Salavert F.
- Garcia-Garcia F.
- Carbonell-Caballero J.
- Bleda M.
- Garcia-Alonso L.
- Sanchis-Juan A.
- Perez-Gil D.
- Marin-Garcia P.
- Sanchez R.
- Cubuk C.
- Hidalgo M.R.
- Amadoz A.
- Hernansaiz-Ballesteros R.D.
- Aleman A.
- Tarraga J.
- Montaner D.
- Medina I.
- Dopazo J.
- Medina I.
- Carbonell J.
- Pulido L.
- Madeira S.C.
- Goetz S.
- Conesa A.
- Tarraga J.
- Pascual-Montano A.
- Nogales-Cadenas R.
- Santoyo J.
- Garcia F.
- Marba M.
- Montaner D.
- Dopazo J.
- Quante M.
- Bhagat G.
- Abrams J.A.
- Marache F.
- Good P.
- Lee M.D.
- Lee Y.
- Friedman R.
- Asfaha S.
- Dubeykovskaya Z.
- Mahmood U.
- Figueiredo J.L.
- Kitajewski J.
- Shawber C.
- Lightdale C.J.
- Rustgi A.K.
- Wang T.C.
- Jonsson T.
- Stefansson H.
- Steinberg S.
- Jonsdottir I.
- Jonsson P.V.
- Snaedal J.
- Bjornsson S.
- Huttenlocher J.
- Levey A.I.
- Lah J.J.
- Rujescu D.
- Hampel H.
- Giegling I.
- Andreassen O.A.
- Engedal K.
- Ulstein I.
- Djurovic S.
- Ibrahim-Verbaas C.
- Hofman A.
- Ikram M.A.
- van Duijn C.M.
- Thorsteinsdottir U.
- Kong A.
- Stefansson K.
- Flinn I.W.
- Bartlett N.L.
- Blum K.A.
- Ardeshna K.M.
- LaCasce A.S.
- Flowers C.R.
- Shustov A.R.
- Thress K.S.
- Mitchell P.
- Zheng F.
- Skolnik J.M.
- Friedberg J.W.
- Weinblatt M.E.
- Kavanaugh A.
- Burgos-Vargas R.
- Dikranian A.H.
- Medrano-Ramirez G.
- Morales-Torres J.L.
- Murphy F.T.
- Musser T.K.
- Straniero N.
- Vicente-Gonzales A.V.
- Grossbard E.
Acknowledgments
References
- The incidence of esophageal adenocarcinoma continues to rise: analysis of period and birth cohort effects on recent trends.Ann Oncol. 2012; 23: 3155-3162
- Cancer statistics, 2010.CA Cancer J Clin. 2010; 60: 277-300
- TP53 gene mutation status in pretreatment biopsies of oesophageal adenocarcinoma has no prognostic value.Eur J Cancer. 1999; 35: 1683-1687
- Comparative genomic analysis of esophageal adenocarcinoma and squamous cell carcinoma.Cancer Discov. 2012; 2: 899-905
- The biomarker TP53 divides patients with neoadjuvantly treated esophageal cancer into 2 subgroups with markedly different outcomes. A p53 Research Group study.J Thorac Cardiovasc Surg. 2014; 148: 2280-2286
- Mutational spectrum of Barrett's stem cells suggests paths to initiation of a precancerous lesion.Nat Commun. 2016; 7: 10380
- The genomic landscape of oesophagogastric junctional adenocarcinoma.J Pathol. 2013; 231: 301-310
- Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity.Nat Genet. 2013; 45: 478-486
- Next-generation sequencing of endoscopic biopsies identifies ARID1A as a tumor-suppressor gene in Barrett's esophagus.Oncogene. 2014; 33: 347-357
- Integrated genomic characterization of oesophageal carcinoma.Nature. 2017; 541: 169-175
- Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis.Nat Genet. 2014; 46: 837-843
- Molecular effects of lapatinib in the treatment of HER2 overexpressing oesophago-gastric adenocarcinoma.Br J Cancer. 2015; 113: 1305-1312
- Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance.Nat Genet. 2016; 48: 1131-1141
- Preexisting oncogenic events impact trastuzumab sensitivity in ERBB2-amplified gastroesophageal adenocarcinoma.J Clin Invest. 2014; 124: 5145-5158
- From reflux esophagitis to esophageal adenocarcinoma.Dig Dis. 2016; 34: 483-490
- Cancer-related inflammation and Barrett's carcinogenesis: interleukin-6 and STAT3 mediate apoptotic resistance in transformed Barrett's cells.Am J Physiol Gastrointest Liver Physiol. 2011; 300: G454-G460
- Association of acute gastroesophageal reflux disease with esophageal histologic changes.JAMA. 2016; 315: 2104-2112
- An integrative genomic approach in oesophageal cells identifies TRB3 as a bile acid responsive gene, downregulated in Barrett's oesophagus, which regulates NF-kappaB activation and cytokine levels.Carcinogenesis. 2010; 31: 936-945
- Low pH induces co-ordinate regulation of gene expression in oesophageal cells.Carcinogenesis. 2006; 27: 319-327
- NF-kappaB activation in esophageal adenocarcinoma: relationship to Barrett's metaplasia, survival, and response to neoadjuvant chemoradiotherapy.Ann Surg. 2004; 239: 491-500
- Activated nuclear factor-kappa B and cytokine profiles in the esophagus parallel tumor regression following neoadjuvant chemoradiotherapy.Dis Esophagus. 2005; 18: 246-252
- Deoxycholate induces COX-2 expression via Erk1/2-, p38-MAPK and AP-1-dependent mechanisms in esophageal cancer cells.BMC Cancer. 2009; 9: 190
- Ursodeoxycholic acid inhibits interleukin 1 beta [corrected] and deoxycholic acid-induced activation of NF-kappaB and AP-1 in human colon cancer cells.Int J Cancer. 2006; 118: 532-539
- NOD-like receptor protein 3 inflammasome priming and activation in Barrett's epithelial cells.Cell Mol Gastroenterol Hepatol. 2016; 2: 439-453
- The characterization of an intestine-like genomic signature maintained during Barrett's-associated adenocarcinogenesis reveals an NR5A2-mediated promotion of cancer cell survival.Sci Rep. 2016; 6: 32638
- An analysis of normalization methods for Drosophila RNAi genomic screens and development of a robust validation scheme.J Biomol Screen. 2008; 13: 777-784
- Web cellHTS2: a web-application for the analysis of high-throughput screening data.BMC Bioinformatics. 2010; 11: 185
- RNAither, an automated pipeline for the statistical analysis of high-throughput RNAi screens.Bioinformatics. 2009; 25: 678-679
- Prognostic biomarkers for esophageal adenocarcinoma identified by analysis of tumor transcriptome.PLoS One. 2010; 5: e15074
- Progression of Barrett's metaplasia to adenocarcinoma is associated with the suppression of the transcriptional programs of epidermal differentiation.Cancer Res. 2005; 65: 3146-3154
- Molecular defense mechanisms of Barrett's metaplasia estimated by an integrative genomics.J Mol Med. 2007; 85: 733-743
- Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research.PLoS Biol. 2010; 8: e1000412
- The Syk inhibitor fostamatinib disodium (R788) inhibits tumor growth in the Emu-TCL1 transgenic mouse model of CLL by blocking antigen-dependent B-cell receptor signaling.Blood. 2010; 116: 4894-4905
- A simple statistical parameter for use in evaluation and validation of high throughput screening assays.J Biomol Screen. 1999; 4: 67-73
- Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.Nat Genet. 2012; 44: 1131-1136
- Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis.Lancet Oncol. 2016; 17: 1363-1373
- ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks.Bioinformatics. 2009; 25: 1091-1093
- All-cause and cancer-specific mortality in GORD in a population-based cohort study (the HUNT study).Gut. 2018; 67: 209-215
- Widespread parainflammation in human cancer.Genome Biol. 2016; 17: 145
- A senescence-inflammatory switch from cancer-inhibitory to cancer-promoting mechanism.Cancer Cell. 2013; 24: 242-256
- The first subcomponent of complement, C1q, triggers the production of IL-8, IL-6, and monocyte chemoattractant peptide-1 by human umbilical vein endothelial cells.J Immunol. 1998; 161: 6924-6930
- In vitro modulation of C1q mRNA expression and secretion by interleukin-1, interleukin-6, and interferon-gamma in resident and stimulated murine peritoneal macrophages.Immunobiology. 2002; 206: 368-376
- Complement protein C1q directs macrophage polarization and limits inflammasome activity during the uptake of apoptotic cells.J Immunol. 2012; 188: 5682-5693
- Phosphorylated Syk expression is enhanced in Nasu-Hakola disease brains.Neuropathology. 2012; 32: 149-157
- Structure, expression pattern and biological activity of molecular complex TREM-2/DAP12.Hum Immunol. 2013; 74: 730-737
- Immune complexes and late complement proteins trigger activation of Syk tyrosine kinase in human CD4(+) T cells.Clin Exp Immunol. 2012; 167: 235-245
- Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1,065 patients.Oncotarget. 2016; 7: 49322-49333
- Bile acid and inflammation activate gastric cardia stem cells in a mouse model of Barrett-like metaplasia.Cancer Cell. 2012; 21: 36-51
- Identification of soluble TREM-2 in the cerebrospinal fluid and its association with multiple sclerosis and CNS inflammation.Brain. 2008; 131: 3081-3091
- Molecular mechanisms for synchronized transcription of three complement C1q subunit genes in dendritic cells and macrophages.J Biol Chem. 2011; 286: 34941-34950
- Canonical Wnt/beta-catenin regulation of liver receptor homolog-1 mediates pluripotency gene expression.Stem Cells. 2010; 28: 1794-1804
- Complement C1q activates canonical Wnt signaling and promotes aging-related phenotypes.Cell. 2012; 149: 1298-1313
- Wnt/beta-catenin signaling contributes to skeletal myopathy in heart failure via direct interaction with forkhead box O.Circ Heart Fail. 2015; 8: 799-808
- Triggering receptor expressed on myeloid cells 2 knockdown exacerbates aging-related neuroinflammation and cognitive deficiency in senescence-accelerated mouse prone 8 mice.Neurobiol Aging. 2014; 35: 1243-1251
- Variant of TREM2 associated with the risk of Alzheimer's disease.N Engl J Med. 2013; 368: 107-116
- TREM2/DAP12 signal elicits proinflammatory response in microglia and exacerbates neuropathic pain.J Neurosci. 2016; 36: 11138-11150
- Treatment of rheumatoid arthritis with a Syk kinase inhibitor: a twelve-week, randomized, placebo-controlled trial.Arthritis Rheum. 2008; 58: 3309-3318
- An oral spleen tyrosine kinase (Syk) inhibitor for rheumatoid arthritis.N Engl J Med. 2010; 363: 1303-1312
- A phase II trial to evaluate the efficacy of fostamatinib in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).Eur J Cancer. 2016; 54: 11-17
- A spleen tyrosine kinase inhibitor reduces the severity of established glomerulonephritis.J Am Soc Nephrol. 2010; 21: 231-236
- In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib.Pharmacol Res Perspect. 2015; 3: e00175
- Cancer cell-autonomous parainflammation mimics immune cell infiltration.Cancer Res. 2017; 77: 3740-3744
- Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma.Science. 2014; 344: 1396-1401
- Targeting homologous recombination and telomerase in Barrett's adenocarcinoma: impact on telomere maintenance, genomic instability and tumor growth.Oncogene. 2014; 33: 1495-1505
- Genomic evolution in Barrett's adenocarcinoma cells: critical roles of elevated hsRAD51, homologous recombination and Alu sequences in the genome.Oncogene. 2011; 30: 3585-3598
- Targeting PI3K and RAD51 in Barrett's adenocarcinoma: impact on DNA damage checkpoints, expression profile and tumor growth.Cancer Genomics Proteomics. 2012; 9: 55-66
- Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus.Gastroenterology. 2015; 148: 367-378
- Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2-3 trial.Lancet Oncol. 2017; 18: 357-370
- Babelomics 5.0: functional interpretation for new generations of genomic data.Nucleic Acids Res. 2015; 43: W117-W121
- Babelomics: an integrative platform for the analysis of transcriptomics, proteomics and genomic data with advanced functional profiling.Nucleic Acids Res. 2010; 38: W210-W213
- Functional complement C1q abnormality leads to impaired immune complexes and apoptotic cell clearance.J Immunol. 2011; 187: 4369-4373
- Antibody neutralization of cell-surface gC1qR/HABP1/SF2-p32 prevents lamellipodia formation and tumorigenesis.Oncotarget. 2016; 7: 49972-49985
- Cell-surface receptor for complement component C1q (gC1qR) is a key regulator for lamellipodia formation and cancer metastasis.J Biol Chem. 2011; 286: 23093-23101
- TREM2 variants: new keys to decipher Alzheimer disease pathogenesis.Nat Rev Neurosci. 2016; 17: 201-207
- Insights into TREM2 biology by network analysis of human brain gene expression data.Neurobiol Aging. 2013; 34: 2699-2714
- Increased cerebrospinal fluid soluble TREM2 concentration in Alzheimer's disease.Mol Neurodegener. 2016; 11: 3
- The triggering receptor expressed on myeloid cells 2: a molecular link of neuroinflammation and neurodegenerative diseases.J Biol Chem. 2016; 291: 4334-4341
- Complement and microglia mediate early synapse loss in Alzheimer mouse models.Science. 2016; 352: 712-716
- The classical complement cascade mediates CNS synapse elimination.Cell. 2007; 131: 1164-1178
- Overexpression of TREM2 enhances glioma cell proliferation and invasion: a therapeutic target in human glioma.Oncotarget. 2016; 7: 2354-2366
- Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer.PLoS One. 2013; 8: e82241
- Fostamatinib, an oral spleen tyrosine kinase inhibitor, in the treatment of rheumatoid arthritis: a meta-analysis of randomized controlled trials.Rheumatol Int. 2016; 36: 1077-1087
- Spleen tyrosine kinase inhibition attenuates autoantibody production and reverses experimental autoimmune GN.J Am Soc Nephrol. 2014; 25: 2291-2302
- Essential role of STAT3 for embryonic stem cell pluripotency.Proc Natl Acad Sci U S A. 1999; 96: 2846-2851
- Jak/Stat3 signaling promotes somatic cell reprogramming by epigenetic regulation.Stem Cells. 2012; 30: 2645-2656
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Footnotes
Author contributions S. P. Duggan and C. Garry performed and designed the studies; F. M. Behan and S. Phipps contributed to technical components of screening implementation; A. Zaheer, M. Kirca, J. V. Reynolds, S. McGarrigle, H. Kudo, R. Goldin, S. E. Kalloger, and D. F. Schaeffer provided clinical and pathologic support and analyses; S. P. Duggan and J. Strid performed and evaluated animal model experiments; A. Long provided in vitro experimental expertise and interpretation; S. P. Duggan and D. Kelleher planned the study design and supervised the study; and all authors edited the manuscript.
Conflicts of interest The authors disclose no conflicts.
Funding Supported by the Health Research Board Ireland (HRB-TRA.2007.11 (S.D., C.G., S.P., D.K., A.L.) and the HRB PhD Scholars program (F.M.B.)), Imperial College London (H.K., R.G., J.S., D.K.), the University of British Columbia Start-up funds F15-04616, and a donation in memoriam by the Chan family (S.D., D.K.).
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