title: Transcribed ultraconserved noncoding RNAs (T-UCR) are involved in Barrett's esophagus carcinogenesis.
abstract: Barrett's esophagus (BE) involves a metaplastic replacement of native esophageal squamous epithelium (Sq) by columnar-intestinalized mucosa, and it is the main risk factor for Barrett-related adenocarcinoma (BAc). Ultra-conserved regions (UCRs) are a class non-coding sequences that are conserved in humans, mice and rats. More than 90% of UCRs are transcribed (T-UCRs) in normal tissues, and are altered at transcriptional level in tumorigenesis. To identify the T-UCR profiles that are dysregulated in Barrett's mucosa transformation, microarray analysis was performed on a discovery set of 51 macro-dissected samples obtained from 14 long-segment BE patients. Results were validated in an independent series of esophageal biopsy/surgery specimens and in two murine models of Barrett's esophagus (i.e. esophagogastric-duodenal anastomosis). Progression from normal to BE to adenocarcinoma was each associated with specific and mutually exclusive T-UCR signatures that included up-regulation of uc.58-, uc.202-, uc.207-, and uc.223- and down-regulation of uc.214+. A 9 T-UCR signature characterized BE versus Sq (with the down-regulation of uc.161-, uc.165-, and uc.327-, and the up-regulation of uc.153-, uc.158-, uc.206-, uc.274-, uc.472-, and uc.473-). Analogous BE-specific T-UCR profiles were shared by human and murine lesions. This study is the first demonstration of a role for T-UCRs in the transformation of Barrett's mucosa.
authors.affiliation: Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy. Department of Surgical Oncology and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy. Comprehensive Cancer Center, Ohio State University, Columbus, OH.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.affiliation: Istituto Oncologico Veneto - IOV-IRCCS, Padua, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Dall'Olmo
authors.affiliation: Department of Morphology and Embryology; University of Ferrara, Ferrara, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Galasso
authors.affiliation: Institute of Cancer Research, London, UK.
authors.forename: Chiara
authors.initials: C
authors.lastname: Braconi
authors.affiliation: Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Pizzi
authors.affiliation: Istituto Oncologico Veneto - IOV-IRCCS, Padua, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Realdon
authors.affiliation: Comprehensive Cancer Center, Ohio State University, Columbus, OH. Department of Morphology and Embryology; University of Ferrara, Ferrara, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Volinia
authors.affiliation: Institute of Cancer Research, London, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Valeri
authors.affiliation: Comprehensive Cancer Center, Ohio State University, Columbus, OH.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Gasparini
authors.affiliation: Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA. Current address: Sanofi, Cambridge, MA, USA.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Baffa
authors.affiliation: Department of Medicine, University of Texas Southwestern Medical Center & VA North Texas Health Care System, Dallas, TX.
authors.forename: Rhonda F
authors.initials: RF
authors.lastname: Souza
authors.affiliation: ARC-NET Research Centre, University of Verona, Verona, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Vicentini
authors.affiliation: Department of Surgical Oncology and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: D'Angelo
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University of Magdeburg, Magdeburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Bornschein
authors.affiliation: Comprehensive Cancer Center, Ohio State University, Columbus, OH.
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Nuovo
authors.affiliation: Department of Surgical Oncology and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Zaninotto
authors.affiliation: Comprehensive Cancer Center, Ohio State University, Columbus, OH.
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
authors.affiliation: Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy. Istituto Oncologico Veneto - IOV-IRCCS, Padua, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
mesh_terms: D000368:Aged; D000818:Animals; D001471:Barrett Esophagus / Q000235:genetics* / Q000473:pathology; D063646:Carcinogenesis; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D022661:RNA, Untranslated / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic
chemical_list: D022661:RNA, Untranslated