Disease relevance of ZMYM2

• FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome [1].
• The t(8;13) atypical myeloproliferative disorder: further analysis of the ZNF198 gene and lack of evidence for multiple genes disrupted on chromosome 13 [2].
• Our results suggest the possibility of a novel gene, distinct from ZNF198, that is located at chromosome 13q12 and involved in the pathogenesis of myelofibrosis [3].
• FIM is related to DXS6673E, a candidate gene for X-linked mental retardation in Xq13.1; this defines a gene family involved in different human pathologies [4].
• OBJECTIVE: To determine the impact of osteoarthritis (OA) on length of rehabilitation stay, Functional Independence Measure (FIM Instrument) ratings at discharge and followup, functional gain, and percentage of patients discharged home [5].

Psychiatry related information on ZMYM2

• Woc is a Drosophila zinc finger protein that shares homology with the human polypeptides ZNF261 and ZNF198 implicated in mental retardation and leukemia syndromes [6].
• As a result of the volume and cost development the direct detrimental effects of alcohol abuse grew from FIM 1.0-1.3 billion in 1980 to FIM 2.8-3.7 billion in 1990: i.e. a real increase of 51-56% in the direct costs of detrimental effects [7].
• These outcomes were corroborated by results of the FIM and the Dementia Rating Scale [8].
• Rehabilitation participation was a mediator of this association: greater depressive symptoms and cognitive impairment predicted poorer rehabilitation participation which, in turn, predicted lower motor FIM efficiency [9].
• Despite similar functional status at inpatient rehabilitation discharge, Hispanic ethnicity was associated with poorer functional outcomes at 1 year postinjury (DRS, FIM, CIQ), after controlling for age, length of posttraumatic amnesia, injury severity, DRS score at admission, FIM score at admission, and preinjury educational level (P<.05) [10].

High impact information on ZMYM2

• Transient expression studies show that the ZNF198-FGFR1 fusion transcript directs the synthesis of an approximately 87-kD polypeptide, localizing predominantly to the cytoplasm [1].
• These translocations are associated with aberrant transcripts in which four predicted zinc-finger domains, contributed by a novel and widely expressed chromosome-13 gene (ZNF198), are fused to the FGFR1 tyrosine-kinase domain [1].
• The syndrome associated with t(8;13)(p11;q12) results in expression of the ZNF198-fibroblast growth factor receptor (FGFR) 1 fusion tyrosine kinase [11].
• Fibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13) [4].
• The ZNF198/FGFR1 fusion kinase associated with an atypical myeloproliferative disease is constitutively activated and regulates several STAT transcription factors [12].

Chemical compound and disease context of ZMYM2

• Further FISH indicated a breakpoint within fibroblast growth factor receptor 1 (FGFR1), the receptor tyrosine kinase that is known to be disrupted in a distinctive myeloproliferative disorder, most commonly by fusion to ZNF198 [13].
• Formalin-fixed, paraffin-embedded tissue sections of 53 colonic adenocarcinomas, 82 adenomas, 46 hyperplastic polyps, and 38 normal colon samples were immunostained with the anti-Glut1 antibody MYM [14].
• In the patient with mitochondrial encephalomyopathy, the FIM score increased from 90 to 103 points over 2 days of tizanidine [15].
• Significant improvement after taking midodrine was reflected in the orthostatic vital signs and symptoms, as well as in FIM instrument scores [16].
• MAIN OUTCOME MEASURES: The Chedoke McMaster Impairment Inventory for arm, hand, postural control, and shoulder pain; Action Research Arm Test; grip strength; and FIM instrument [17].

Biological context of ZMYM2

• Exon trapping of a PAC that spanned the chromosome 13 translocation breakpoints led to the identification of a gene, ZNF198, that detected rearranged bands when used as a probe against Southern blots of patient DNA [18].
• Sequencing of these products revealed that ZNF198 consists of 26 exons with the initiation codon located in exon 4 [19].
• These observations support the idea that ZNF198, through its interaction with HHR6 and RAD18, may be involved in the DNA repair process [20].
• These observations suggest that expression of the ZNF198/FGFR1 fusion gene is associated with specific PAI-2-mediated resistance to apoptosis which may contribute to the highly malignant nature of leukemic cells carrying this fusion kinase gene [12].
• We used oligonucleotide microarrays to compare the gene-expression profiles between HEK-293 cells that stably express either the ZNF198/FGFR1 chimeric protein or the wild-type ZNF198 gene [12].

Anatomical context of ZMYM2

• Consistent fusion of ZNF198 to the fibroblast growth factor receptor-1 in the t(8;13)(p11;q12) myeloproliferative syndrome [18].
• To determine the transforming properties of this chimeric protein we transfected ZNF198-FGFR1 into the interleukin (IL)-3 dependent cell line Ba/F3 [21].
• Patients with combined lesions and more extensive brain injury had significantly higher FIM scores (P < 0.05) than patients with injury restricted to the basal ganglia/ internal capsule [22].
• 3. Ramp stretches (0.5-8.6% sarcomere strain, confined to the plateau of the isometric tension-length relationship) were given at different velocities of lengthening (0.03-1.8 sarcomere lengths s-1) [23].
• Hierarchical linear modeling of FIM instrument growth curve characteristics after spinal cord injury [24].

Associations of ZMYM2 with chemical compounds

• Arsenic trioxide reduced STAT3 activation by Janus kinases, altered phosphorylation and electrophoretic mobility of ZNF198/fibroblast growth factor receptor 1, reduced kinase protein level, and decreased STAT3 protein phosphorylation [25].
• The bactericidal effect of a combination of rifampin (Ramp) and trimethoprim (Tmp) was studied using dense cultures of test organisms, including some urinary pathogens, growing in human urine [26].
• 5-fluorouracil, ifosfamide and mitomycin (FIM) combination for pancreatic-biliary tumors [27].
• Using the muscle relaxant with the longest waiting time instead of that with the shortest waiting time (difference 21.8 min) cost more than FIM 800 (approximately $160) extra per patient [28].
• Patients with CHF performed a maximal exercise test using a Ramp protocol before and after 6 months of therapy with either metoprolol or carvedilol [29].

Regulatory relationships of ZMYM2

• We also show that forced expression of FIM inhibits the emergence of hematopoietic cells in the cultured mouse aorta-gonad-mesonephros (AGM) region on embryonic day (E) 11.5, where definitive hematopoiesis is first found during embryogenesis [30].

Other interactions of ZMYM2

• Clones were identified in which the ZNF198 was fused to exon 9 of the fibroblast growth factor receptor-1 (FGFR1), a gene known to map to 8p11 [18].
• We demonstrate here that the human RAD18 is also present in the ZNF198/HHR6 protein complex, although it does not coimmunoprecipitate with the fusion kinase [20].
• Replacement of the ZNF198 portion by the Bcr portion as present in the t(8;22) translocation shifted the signaling toward a more prominent STAT5 activation [31].
• The reciprocal t(8;13) chromosome translocation results in a fusion gene (FUS) in which the N-terminal half of the zinc finger protein ZNF198 is combined with the cytoplasmic domain of the fibroblast growth factor receptor-1 (FGFR1) [31].
• These observations were confirmed using co-immunoprecipitation which demonstrated that ZNF198 is covalently modified by SUMO-1 [32].

Analytical, diagnostic and therapeutic context of ZMYM2

• To identify the translocation partner gene on chromosome 8, 5' and 3' RACE polymerase chain reactions (PCRs) were performed on patient RNA with several combinations of ZNF198 primers [18].
• Rearrangements of both ZNF198 and FGFR1 were found in two further patients by Southern blotting [18].
• Immunoprecipitation analysis revealed that both intracellular forms of PAI-2 bind to the ZNF198/FGFR1 kinase [12].
• The interaction between TLS/FUS and ZNF198 was confirmed using Western blot analysis [33].
• Outcome variables were length of stay, FIM Instrument ratings at discharge and followup, functional gain, and percentage of patients discharged home [5].

References