title: KAT6B Is a Tumor Suppressor Histone H3 Lysine 23 Acetyltransferase Undergoing Genomic Loss in Small Cell Lung Cancer.
abstract: Recent efforts to sequence human cancer genomes have highlighted that point mutations in genes involved in the epigenetic setting occur in tumor cells. Small cell lung cancer (SCLC) is an aggressive tumor with poor prognosis, where little is known about the genetic events related to its development. Herein, we have identified the presence of homozygous deletions of the candidate histone acetyltransferase KAT6B, and the loss of the corresponding transcript, in SCLC cell lines and primary tumors. Furthermore, we show, in vitro and in vivo, that the depletion of KAT6B expression enhances cancer growth, while its restoration induces tumor suppressor-like features. Most importantly, we demonstrate that KAT6B exerts its tumor-inhibitory role through a newly defined type of histone H3 Lys23 acetyltransferase activity.
authors.affiliation: Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Catalonia, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Simó-Riudalbas
authors.affiliation: Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Catalonia, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Pérez-Salvia
authors.affiliation: Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Catalonia, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Setien
authors.affiliation: Translational Research Laboratory, Catalan Institute of Oncology (ICO), IDIBELL, Barcelona, Catalonia, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Villanueva
authors.affiliation: Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Catalonia, Spain.
authors.forename: Catia
authors.initials: C
authors.lastname: Moutinho
authors.affiliation: Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Catalonia, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Martínez-Cardús
authors.affiliation: Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Catalonia, Spain.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Moran
authors.affiliation: Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Catalonia, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Berdasco
authors.affiliation: Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Catalonia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gomez
authors.affiliation: Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Catalonia, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Vidal
authors.affiliation: Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Catalonia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Soler
authors.affiliation: Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Catalonia, Spain.
authors.forename: Holger
authors.initials: H
authors.lastname: Heyn
authors.affiliation: Chromatin Biology Group, IDIBELL, Barcelona, Catalonia, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Vaquero
authors.affiliation: Proteomics Unit at PEBC, IDIBELL, Barcelona, Catalonia, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: de la Torre
authors.affiliation: Proteomics Unit at PEBC, IDIBELL, Barcelona, Catalonia, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Barceló-Batllori
authors.affiliation: Department of Pathology, Bellvitge University Hospital, IDIBELL, Barcelona, Catalonia, Spain.
authors.forename: August
authors.initials: A
authors.lastname: Vidal
authors.affiliation: Tumor Genomics Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Roz
authors.affiliation: Thoracic Surgery Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: Pastorino
authors.affiliation: Institute of Pediatrics, Clinical Genetics Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Szakszon
authors.affiliation: Institute of Human Genetics, University of Ulm, Ulm, Germany.
authors.forename: Guntram
authors.initials: G
authors.lastname: Borck
authors.affiliation: Department of Pathology, Centro Hospitalar de São João, Porto, Portugal.
authors.forename: Conceição S
authors.initials: CS
authors.lastname: Moura
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) and Medical Faculty of University of Porto, Porto, Portugal.
authors.forename: Fátima
authors.initials: F
authors.lastname: Carneiro
authors.affiliation: MRC-Holland, Amsterdam, the Netherlands.
authors.forename: Ilse
authors.initials: I
authors.lastname: Zondervan
authors.affiliation: MRC-Holland, Amsterdam, the Netherlands.
authors.forename: Suvi
authors.initials: S
authors.lastname: Savola
authors.affiliation: Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Reika
authors.initials: R
authors.lastname: Iwakawa
authors.affiliation: Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.affiliation: Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan. Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Badalona, Catalonia, Spain.
authors.forename: Jun
authors.initials: J
authors.lastname: Yokota
authors.affiliation: Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Catalonia, Spain. Department of Physiological Sciences II, School of Medicine, University of Barcelona, Barcelona, Catalonia, Spain. Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain. mesteller@idibell.cat.
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
mesh_terms: D000107:Acetylation; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D019008:Drug Resistance, Neoplasm; D017353:Gene Deletion; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D064593:Heterografts; D051548:Histone Acetyltransferases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: D018906:Antineoplastic Agents, Alkylating; D006657:Histones; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D000077146:Irinotecan; D051548:Histone Acetyltransferases; C487137:KAT6B protein, human; D002166:Camptothecin