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Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Gene Section Short Communication RPRM (reprimo, TP53 dependent G2 arrest mediator candidate) Alejandro H Corvalan, Veronica A Torres Laboratory of Molecular Pathology and Epidemiology, Department of Hemathology - Oncology, School of Medicine - P Universidad Catolica de Chile, 391 Marcoleta St - Santiago 8330074 Chile (AHC, TorresVAT) Published in Atlas Database: November 2011 Online updated version : http://AtlasGeneticsOncology.org/Genes/RPRMID42082ch2q23.html DOI: 10.4267/2042/47283 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2012 Atlas of Genetics and Cytogenetics in Oncology and Haematology in the cytoplasm. Identity Function Other names: FLJ90327, REPRIMO HGNC (Hugo): RPRM Location: 2q23.3 DNA/RNA Reprimo is a candidate tumor suppresor gene involved in the G2/M phase cell cycle arrest mediated by tumor protein p53. Reprimo induces cell cycle arrest by inhibiting the nuclear translocation of the Cdc2-Cyclin B1 complex. Description Implicated in Reprimo gene consists of 1 exon. The gene spans 1,47 kb of genomic DNA on the chromosome 2 in the minus strand. Various cancers Note The aberrant methylation of the promoter region of Reprimo is a common event that may contribute to the pathogenesis of some types of human cancer. Promoter methylation of Reprimo was found in pancreatic cancer (91%), gastric cancer (90%), gallbladder cancer (62%), lymphomas (57%), colorectal cancer (56%) and esophageal adenocarcinomas (40%). In breast cancer, leukemias and lung cancer, promoter methylation of Reprimo was found in less than 40% of tested cases. Transcription The mRNA is 1496 bp in length. Protein Description The open reading frame encodes a 109 amino acid protein with an estimated molecular weight of 11774 Da. Reprimo is a highly glycosylated protein which has two sites in amino acids 7 and 18. The protein has a potential transmembrane site covering amino acids 56 to 76. Gastric cancer Disease Aberrant hypermethylation of Reprimo is frequently found in primary gastric cancer as well as in pair plasma samples. In plasma from asymptomatic controls, Reprimo is infrequently methylated. Therefore, plasmatic detection of Reprimo is a putative biomarker for early detection of gastric cancer. Expression The expression of Reprimo is induced by tumor protein p53 following X-ray irradiation. Localisation When Reprimo is ectopically expressed, it is localized Atlas Genet Cytogenet Oncol Haematol. 2012; 16(3) 223 RPRM (reprimo, TP53 dependent G2 arrest mediator candidate) Corvalan AH, TorresVA The above histogram represents the percentage of positive cases for Reprimo and other genes (APC, SHP1, CDH-1, ER, SEMA3B and 3OST2) in 43 prospectively collected gastric cancer cases and 31 asymptomatic age- and gender-matched controls. Only Reprimo shows a significant difference in plasma between gastric cancer and asymptomatic controls (Bernal et al., Clin Cancer Res. 2008;14:6264-9). Takahashi T, Suzuki M, Shigematsu H, Shivapurkar N, Echebiri C, Nomura M, Stastny V, Augustus M, Wu CW, Wistuba II, Meltzer SJ, Gazdar AF. Aberrant methylation of Reprimo in human malignancies. Int J Cancer. 2005 Jul 1;115(4):503-10 Pancreatic cancer Disease Aberrant hypermethylation of Reprimo is also common in pancreatic cell lines (91%) and in pancreatic adenocarcinomas (66%). Reprimo methylation is correlated with poor prognosis in a large series of resected pancreatic cancers. This fact raises the possibility that aberrant methylation of Reprimo is an epigenetic event that may have a mechanistic role in pancreatic cancer. Hamilton JP, Sato F, Jin Z, Greenwald BD, Ito T, Mori Y, Paun BC, Kan T, Cheng Y, Wang S, Yang J, Abraham JM, Meltzer SJ. Reprimo methylation is a potential biomarker of Barrett'sAssociated esophageal neoplastic progression. Clin Cancer Res. 2006 Nov 15;12(22):6637-42 Sato N, Fukushima N, Matsubayashi H, Iacobuzio-Donahue CA, Yeo CJ, Goggins M. Aberrant methylation of Reprimo correlates with genetic instability and predicts poor prognosis in pancreatic ductal adenocarcinoma. Cancer. 2006 Jul 15;107(2):251-7 References Ohki R, Nemoto J, Murasawa H, Oda E, Inazawa J, Tanaka N, Taniguchi T. Reprimo, a new candidate mediator of the p53mediated cell cycle arrest at the G2 phase. J Biol Chem. 2000 Jul 28;275(30):22627-30 Bernal C, Aguayo F, Villarroel C, Vargas M, Díaz I, Ossandon FJ, Santibáñez E, Palma M, Aravena E, Barrientos C, Corvalan AH. Reprimo as a potential biomarker for early detection in gastric cancer. Clin Cancer Res. 2008 Oct 1;14(19):6264-9 Sato N, Fukushima N, Maitra A, Matsubayashi H, Yeo CJ, Cameron JL, Hruban RH, Goggins M. Discovery of novel targets for aberrant methylation in pancreatic carcinoma using high-throughput microarrays. Cancer Res. 2003 Jul 1;63(13):3735-42 This article should be referenced as such: Corvalan AH, TorresVA. RPRM (reprimo, TP53 dependent G2 arrest mediator candidate). Atlas Genet Cytogenet Oncol Haematol. 2012; 16(3):223-224. Suzuki M, Shigematsu H, Takahashi T, Shivapurkar N, Sathyanarayana UG, Iizasa T, Fujisawa T, Gazdar AF. Aberrant methylation of Reprimo in lung cancer. Lung Cancer. 2005 Mar;47(3):309-14 Atlas Genet Cytogenet Oncol Haematol. 2012; 16(3) 224