| Written | 2014-04 | Joel Fulton, David M Heery |
| Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK |
| Identity |
| Alias_names | MAPE |
| Alias_symbol (synonym) | CT130 |
| Other alias | OIP-4 |
| OIP4 | |
| HGNC (Hugo) | PRAME |
| LocusID (NCBI) | 23532 |
| Atlas_Id | 41828 |
| Location | 22q11.22 [Link to chromosome band 22q11] |
| Location_base_pair | Starts at 22547696 and ends at 22557754 bp from pter ( according to hg19-Feb_2009) [Mapping PRAME.png] |
| Fusion genes (updated 2016) | PRAME (22q11.22) / ACO2 (22q13.2) | PRAME (22q11.22) / GDI2 (10p15.1) | PRAME (22q11.22) / HDLBP (2q37.3) |
| DNA/RNA |
| Note | PRAME is a member of a multigene family present in humans and other mammals. It was originally identified as a gene encoding a novel cancer-testis antigen that is over expressed in melanoma (Ikeda et al., 1997). Its evolution is consistent with adaptive (positive) selection similar to gene clusters involved in immunity and reproduction, such as the NALP family (Tian et al., 2009). Expression of PRAME has been shown to be regulated by hypomethylation of its promoter in AML and CML (Ortmann et al., 2008; Roman-Gomez et al., 2007). |
| Description | The gene is encoded on the reverse strand of chromosome 22 (22q11.22) covering a region of approximately 12 kilobases and is within the human immunoglobulin lambda gene locus (Kawasaki et al., 1997). This locus contains a large number of Vl gene segments which code for production of l light chains during B cell development and several other non-immunoglobulin genes, for example, tandem Suppressor of Hairy Wing genes (SUHW1/ZNF280A and SUHW2/ZNF280B) and a gene encoding a putative membrane glycoprotein (POM121L1). |
| Transcription | The NCBI database annotates five PRAME mRNA transcripts ranging from 2.1-2.7 kb in length (2141, 2162, 2197, 2220, 2776 bases) which encode the same protein. Transcript (Including UTRs): - Position: chr22:22890123-22896603, Size: 6481, Total exon count: 4 - Strand: - Coding region: - Position: chr22:22890489-22893484, Size: 2996, Coding exon count: 3 |
| Pseudogene | The gene seems to have undergone multiple duplications during hominid evolution, and at least 22 PRAME-like genes and 10 pseudogenes have been identified in the human genome (Birtle et al., 2005). |
| Protein |
| Note | PRAME is a leucine-rich protein of which 21.8% of residues are leucine or isoleucine. |
 | |
| Predicted domain structure of the human PRAME sequence highlighting Leucine Rich Repeats (LRRs). The LRRs are numbered and indicated by the blue arrows; residues conserved in typical LRRs are highlighted in bold. The black boxes indicate regions predicted to have a high probability of α-helicity, and two predicted NLS sequences are underlined. The boxed area in red is a region implicated in interaction with retinoic acid receptors (Wadelin et al., 2010). | |
| Description | NP_006106 : Predicted 509 amino acid, 58 kDa protein. |
| Expression | PRAME is expressed at low levels in a few normal tissues, at intermediate level in adrenals, ovary, and endometrium and at high level in the testes. It has been shown to be overexpressed in malignant cells including the vast majority of primary and metastatic melanomas and is recognized by cytolytic T lymphocytes (Haqq et al., 2005). In PRAME-negative leukaemias the gene can be induced by demethylating agents (Sigalotti et al., 2004). |
| Localisation | The protein has been observed to localise to both the nucleus and perinuclear regions (Tajeddine et al., 2005). PRAME contains several candidate nuclear localisation signal (NLS) sequences (See Figure). |
| Function | Human PRAME and its paralogues are related to LRR family proteins, some of which are known to have functions in cell immunity and signal transduction. It has been suggested that, like TLRs, PRAME may be upregulated in response to encounters with microbial pathogens, and may be involved in targeting intracellular PAMPs to the Golgi for ubiquitylation and processing. (Wadelin et al., 2013). PRAME has been reported to function as a repressor of retinoic acid (RA) signalling through interactions with retinoic acid receptors (RARs) and repression of the RARb2 gene (Epping et al., 2005; Epping et al., 2007). |
| Homology | Sequence homology and structural predictions suggest that PRAME is related to the leucine-rich repeat (LRR) family of proteins such as the Toll-like receptors. The Oogenesins 1-4 also show considerable homology to PRAME and PRAME family members (Dade et al., 2003). |
| Mutations |
| Note | Some listed in COSMIC. |
| Implicated in |
| Note | |
| Entity | Melanoma |
| Note | High levels of PRAME mRNA are present in the majority of primary and metastatic melanomas (88% and 95% respectively) (Haqq et al., 2005), while being absent in normal haematopoietic tissues including bone marrow (Oehler et al., 2009; Radich et al., 2006; Steinbach et al., 2002; van Baren et al., 1998). |
| Entity | Acute and chronic leukaemia, non Hodgkins lymphomas |
| Note | Numerous studies have reported highly elevated levels of PRAME in both acute and chronic leukaemias and non Hodgkin's lymphomas (van Baren et al., 1998; Matsushita et al., 2001; Oehler et al., 2009; Qin et al., 2009; Radich et al., 2006; Santamaria et al., 2008). PRAME expression has been suggested to be predicator for a good clinical outcome in childhood acute lymphoblastic leukemia in addition to being a target for immunotherapy, and biomarker for the monitoring of minimal residual disease (Abdelmalak et al., 2014). |
| Entity | Neuroblastoma |
| Note | PRAME is expressed in high-stage neuroblastoma and associated with poor outcome (Oberthuer et al., 2004). |
| Entity | Breast cancer |
| Note | PRAME is expressed in advanced breast cancer and has been shown to be an independent prognostic factor for shortened disease-free survival (Doolan et al., 2008). |
| Entity | Ovarian adenocarcinoma |
| Note | PRAME was found to be a biomarker and prognostic factor for patients with stage III serous ovarian adenocarcinomas (Partheen et al., 2008). |
| Entity | Lung squamous cell carcinoma |
| Note | Northern blot analysis demonstrated that high proportion of positive tumours were shown to express PRAME (Ikeda et al., 1997). |
| Entity | Head and neck cancer |
| Note | Reverse-transcriptase polymerase chain reaction (RT-PCR) showed high expression of the gene coding for the tumor antigen PRAME in surgical samples of the tumors, margins, and lymph nodes from patients with a diagnosis of head and neck carcinoma (Figueiredo et al., 2006). |
| Entity | Neurological neoplasms |
| Note | PRAME has been identified as a potential CT antigen for medulloblastoma (Boon et al., 2003) and is universally expressed in high-stage neuroblastoma, and has been associated with poor outcome (Oberthuer et al., 2004). |
| Bibliography |
| PRAME gene expression in childhood acute lymphoblastic leukemia: impact on prognosis. |
| Abdelmalak CA, Yahya RS, Elghannam DM, El-Khadragy AE, Abd El Messih HM. |
| Clin Lab. 2014;60(1):55-61. |
| PMID 24600975 |
| Duplication and positive selection among hominin-specific PRAME genes. |
| Birtle Z, Goodstadt L, Ponting C. |
| BMC Genomics. 2005 Sep 13;6:120. |
| PMID 16159394 |
| Comparison of medulloblastoma and normal neural transcriptomes identifies a restricted set of activated genes. |
| Boon K, Edwards JB, Siu IM, Olschner D, Eberhart CG, Marra MA, Strausberg RL, Riggins GJ. |
| Oncogene. 2003 Oct 23;22(48):7687-94. |
| PMID 14576832 |
| Identification of a new expanding family of genes characterized by atypical LRR domains. Localization of a cluster preferentially expressed in oocyte. |
| Dade S, Callebaut I, Mermillod P, Monget P. |
| FEBS Lett. 2003 Dec 18;555(3):533-8. |
| PMID 14675769 |
| Prevalence and prognostic and predictive relevance of PRAME in breast cancer. |
| Doolan P, Clynes M, Kennedy S, Mehta JP, Crown J, O'Driscoll L. |
| Breast Cancer Res Treat. 2008 May;109(2):359-65. Epub 2007 Jul 12. |
| PMID 17624586 |
| A functional genetic screen identifies retinoic acid signaling as a target of histone deacetylase inhibitors. |
| Epping MT, Wang L, Plumb JA, Lieb M, Gronemeyer H, Brown R, Bernards R. |
| Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17777-82. Epub 2007 Oct 29. |
| PMID 17968018 |
| Expression of cancer testis antigens in head and neck squamous cell carcinomas. |
| Figueiredo DL, Mamede RC, Proto-Siqueira R, Neder L, Silva WA Jr, Zago MA. |
| Head Neck. 2006 Jul;28(7):614-9. |
| PMID 16475205 |
| The gene expression signatures of melanoma progression. |
| Haqq C, Nosrati M, Sudilovsky D, Crothers J, Khodabakhsh D, Pulliam BL, Federman S, Miller JR 3rd, Allen RE, Singer MI, Leong SP, Ljung BM, Sagebiel RW, Kashani-Sabet M. |
| Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):6092-7. Epub 2005 Apr 15. |
| PMID 15833814 |
| Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor. |
| Ikeda H, Lethe B, Lehmann F, van Baren N, Baurain JF, de Smet C, Chambost H, Vitale M, Moretta A, Boon T, Coulie PG. |
| Immunity. 1997 Feb;6(2):199-208. |
| PMID 9047241 |
| One-megabase sequence analysis of the human immunoglobulin lambda gene locus |
| Kawasaki K, Minoshima S, Nakato E, Shibuya K, Shintani A, Schmeits JL, Wang J, Shimizu N. |
| Genome Res. 1997 Mar;7(3):250-61. |
| PMID 9074928 |
| Quantitative monitoring of the PRAME gene for the detection of minimal residual disease in leukaemia. |
| Matsushita M, Ikeda H, Kizaki M, Okamoto S, Ogasawara M, Ikeda Y, Kawakami Y. |
| Br J Haematol. 2001 Mar;112(4):916-26. |
| PMID 11298586 |
| The tumor-associated antigen PRAME is universally expressed in high-stage neuroblastoma and associated with poor outcome. |
| Oberthuer A, Hero B, Spitz R, Berthold F, Fischer M. |
| Clin Cancer Res. 2004 Jul 1;10(13):4307-13. |
| PMID 15240516 |
| The preferentially expressed antigen in melanoma (PRAME) inhibits myeloid differentiation in normal hematopoietic and leukemic progenitor cells. |
| Oehler VG, Guthrie KA, Cummings CL, Sabo K, Wood BL, Gooley T, Yang T, Epping MT, Shou Y, Pogosova-Agadjanyan E, Ladne P, Stirewalt DL, Abkowitz JL, Radich JP. |
| Blood. 2009 Oct 8;114(15):3299-308. doi: 10.1182/blood-2008-07-170282. Epub 2009 Jul 22. |
| PMID 19625708 |
| Aberrant hypomethylation of the cancer-testis antigen PRAME correlates with PRAME expression in acute myeloid leukemia. |
| Ortmann CA, Eisele L, Nuckel H, Klein-Hitpass L, Fuhrer A, Duhrsen U, Zeschnigk M. |
| Ann Hematol. 2008 Oct;87(10):809-18. doi: 10.1007/s00277-008-0514-8. Epub 2008 Jun 28. |
| PMID 18587578 |
| Four potential biomarkers as prognostic factors in stage III serous ovarian adenocarcinomas. |
| Partheen K, Levan K, Osterberg L, Claesson I, Fallenius G, Sundfeldt K, Horvath G. |
| Int J Cancer. 2008 Nov 1;123(9):2130-7. doi: 10.1002/ijc.23758. |
| PMID 18709641 |
| Expression patterns of WT1 and PRAME in acute myeloid leukemia patients and their usefulness for monitoring minimal residual disease. |
| Qin Y, Zhu H, Jiang B, Li J, Lu X, Li L, Ruan G, Liu Y, Chen S, Huang X. |
| Leuk Res. 2009 Mar;33(3):384-90. doi: 10.1016/j.leukres.2008.08.026. Epub 2008 Oct 23. |
| PMID 18950857 |
| Gene expression changes associated with progression and response in chronic myeloid leukemia. |
| Radich JP, Dai H, Mao M, Oehler V, Schelter J, Druker B, Sawyers C, Shah N, Stock W, Willman CL, Friend S, Linsley PS. |
| Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2794-9. Epub 2006 Feb 13. |
| PMID 16477019 |
| Epigenetic regulation of PRAME gene in chronic myeloid leukemia. |
| Roman-Gomez J, Jimenez-Velasco A, Agirre X, Castillejo JA, Navarro G, Jose-Eneriz ES, Garate L, Cordeu L, Cervantes F, Prosper F, Heiniger A, Torres A. |
| Leuk Res. 2007 Nov;31(11):1521-8. Epub 2007 Mar 26. |
| PMID 17382387 |
| The relevance of preferentially expressed antigen of melanoma (PRAME) as a marker of disease activity and prognosis in acute promyelocytic leukemia. |
| Santamaria C, Chillon MC, Garcia-Sanz R, Balanzategui A, Sarasquete ME, Alcoceba M, Ramos F, Bernal T, Queizan JA, Penarrubia MJ, Giraldo P, San Miguel JF, Gonzalez M. |
| Haematologica. 2008 Dec;93(12):1797-805. doi: 10.3324/haematol.13214. Epub 2008 Sep 24. |
| PMID 18815192 |
| Intratumor heterogeneity of cancer/testis antigens expression in human cutaneous melanoma is methylation-regulated and functionally reverted by 5-aza-2'-deoxycytidine. |
| Sigalotti L, Fratta E, Coral S, Tanzarella S, Danielli R, Colizzi F, Fonsatti E, Traversari C, Altomonte M, Maio M. |
| Cancer Res. 2004 Dec 15;64(24):9167-71. |
| PMID 15604288 |
| PRAME gene expression in childhood acute lymphoblastic leukemia. |
| Steinbach D, Viehmann S, Zintl F, Gruhn B. |
| Cancer Genet Cytogenet. 2002 Oct 1;138(1):89-91. |
| PMID 12419593 |
| Tumor-associated antigen preferentially expressed antigen of melanoma (PRAME) induces caspase-independent cell death in vitro and reduces tumorigenicity in vivo. |
| Tajeddine N, Gala JL, Louis M, Van Schoor M, Tombal B, Gailly P. |
| Cancer Res. 2005 Aug 15;65(16):7348-55. |
| PMID 16103086 |
| Evolution and functional divergence of NLRP genes in mammalian reproductive systems. |
| Tian X, Pascal G, Monget P. |
| BMC Evol Biol. 2009 Aug 14;9:202. doi: 10.1186/1471-2148-9-202. |
| PMID 19682372 |
| Leucine-rich repeat protein PRAME: expression, potential functions and clinical implications for leukaemia. |
| Wadelin F, Fulton J, McEwan PA, Spriggs KA, Emsley J, Heery DM. |
| Mol Cancer. 2010 Aug 27;9:226. doi: 10.1186/1476-4598-9-226. (REVIEW) |
| PMID 20799951 |
| PRAME is a golgi-targeted protein that associates with the Elongin BC complex and is upregulated by interferon-gamma and bacterial PAMPs. |
| Wadelin FR, Fulton J, Collins HM, Tertipis N, Bottley A, Spriggs KA, Falcone FH, Heery DM. |
| PLoS One. 2013;8(2):e58052. doi: 10.1371/journal.pone.0058052. Epub 2013 Feb 27. |
| PMID 23460923 |
| PRAME, a gene encoding an antigen recognized on a human melanoma by cytolytic T cells, is expressed in acute leukaemia cells. |
| van Baren N, Chambost H, Ferrant A, Michaux L, Ikeda H, Millard I, Olive D, Boon T, Coulie PG. |
| Br J Haematol. 1998 Sep;102(5):1376-9. |
| PMID 9753074 |
| Citation |
| This paper should be referenced as such : |
| J Fulton, DM Heery |
| PRAME (Preferentially Expressed Antigen In Melanoma) |
| Atlas Genet Cytogenet Oncol Haematol. 2014;18(12):941-944. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/PRAMEID41828ch22q11.html |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Fri Jun 30 11:15:31 CEST 2017 |
For comments and suggestions or contributions, please contact us