title: Delineation of known and new transcript variants of the SETMAR (Metnase) gene and the expression profile in hematologic neoplasms.
abstract: SET domain and mariner transposase fusion gene (SETMAR), also known as Metnase, has previously been shown to suppress the formation of chromosomal translocation in mouse fibroblasts. Despite the fact that hematologic malignancies are often characterized by chromosomal rearrangements, no studies have hitherto investigated the expression pattern of the gene in these disorders. We hypothesized that a high expression of SETMAR protected the cells from chromosomal rearrangements; thus, we examined the mRNA expression of SETMAR transcript variants in hematologic patients. We identified six transcript variants (var1, var2, var5, varA, varB, varC), of which three had not been reported previously. Expression levels were quantified by transcript-specific quantitative polymerase chain reaction in 15 healthy individuals, 70 acute myeloid leukemia (AML) patients (translocation positive, n= 30 [AML(TPos)], translocation negative, n = 40 [AML(TNeg)]), seven patients with mantle cell lymphoma (t [11,14] positive), and 13 patients with chronic myeloid leukemia (t [9,22] positive). All variants were significantly overexpressed in both subgroups of AML compared with healthy individuals (var1 and var2: p < 0.00001 for both AML subgroups, varA and varB: p = 0.0002, var5: p = 0.0008, and varC: p = 0.0001 for AML(TNeg); varA: p = 0.0048, varB and var5: p = 0.0001, varC: p = 0.0017). When comparing the expression in AML(TNeg) and AML(TPos), we found a significantly increased expression of the full length SETMAR in AML(TNeg) (var1: p = 0.047), suggesting a protective effect of high SETMAR expression on formation of chromosomal translocations. In conclusion, we have found known and novel SETMAR splice variants to be significantly increased in AML. To our knowledge, this is the first study that describes an expression profile of SETMAR in subgroups of hematologic malignancies, which can be linked to the incidence of chromosomal rearrangements.
authors.affiliation: Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Dinisha Cyril
authors.initials: DC
authors.lastname: Jeyaratnam
authors.affiliation: Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Benjamin Stephan
authors.initials: BS
authors.lastname: Baduin
authors.affiliation: Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Marcus Celik
authors.initials: MC
authors.lastname: Hansen
authors.affiliation: Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Hansen
authors.affiliation: Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Judit Meszaros
authors.initials: JM
authors.lastname: Jørgensen
authors.affiliation: Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Anni
authors.initials: A
authors.lastname: Aggerholm
authors.affiliation: Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Hans Beier
authors.initials: HB
authors.lastname: Ommen
authors.affiliation: Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Hokland
authors.affiliation: Department of Hematology, Aarhus University Hospital, Aarhus, Denmark. Electronic address: nyvold@ki.au.dk.
authors.forename: Charlotte Guldborg
authors.initials: CG
authors.lastname: Nyvold
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D045643:DNA Repair Enzymes / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D019337:Hematologic Neoplasms / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D000072260:RNA Splicing Factors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; D012333:RNA, Messenger; D011495:Histone-Lysine N-Methyltransferase; C510450:SETMAR protein, human; D045643:DNA Repair Enzymes; C417041:PRPF19 protein, human