| Written | 2011-08 | Norihisa Saeki, Hiroki Sasaki |
| Genetics Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan |
| Identity |
| Alias (NCBI) | rhombotin 1 | RBTN1 | RHOM1 | TTG1 |
| HGNC (Hugo) | LMO1 |
| HGNC Alias symb | TTG1 | RHOM1 |
| HGNC Previous name | RBTN1 |
| HGNC Previous name | rhombotin 1 |
| LocusID (NCBI) | 4004 |
| Atlas_Id | 33 |
| Location | 11p15.4 [Link to chromosome band 11p15] |
| Location_base_pair | Starts at 8224309 and ends at 8263878 bp from pter ( according to hg19-Feb_2009) [Mapping LMO1.png] |
| Local_order | Telomeric to STK33 gene; centromeric to RIC3 gene. |
 | |
| LMO1 gene is located between RIC3 and STK33 genes in Chromosome 11p15. The arrow indicates the orientation of the genes. | |
| Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
| C2CD5 (12p12.1) / LMO1 (11p15.4) | LMO1 (11p15.4) / SPACA6 (19q13.41) | TRBV20OR9-2 (-) / LMO1 (11p15.4) | |
| DNA/RNA |
 | |
| Structure of LMO1 gene. The gene consists of 5 exons and several splicing variants were reported. | |
| Description | 4,4 kb (from the beginning of the 1st exon to the end of the 5th exon) consisting of 5 exons. |
| Transcription | mRNA of approximately 700 - 1000 bp, depending on the splicing variants. |
| Pseudogene | Not reported. |
| Protein |
| Description | The protein contains two highly conserved, cysteine-rich motifs known as LIM domains, which interact with other proteins. As LMO1 has no DNA-binding domain, its DNA binding ability is dependent on the other proteins with which it interacts. The proteins known for binding to LMO1 include TAL1/SCL and LDB1, and the molecules have an oncogenic function in T cell acute leukemia with the chromosomal translocation t(11;14)(p15;q11). |
| Expression | LMO1 expression is prominent in the central nervous system in both human and mouse. In mice it was observed by an in situ hybridization technique in the cerebral cortex, diencephalon, mesencephalon, cerebellum, myeloencephalon and spinal cord. Northern blot analysis revealed its expression in the thymus, kidney and placenta of adult mice. |
| Localisation | Nucleus. |
| Function | Transcription factor. |
| Mutations |
| Note | Not reported. |
| Implicated in |
| Note | |
| Entity | Neuroblastoma |
| Disease | Genome-wide association studies revealed a corelation between neuroblastoma and a single nucleotide polymorphism in LMO1 gene, rs110419 (A/G), of which the A allele was shown to promote LMO1 expression and to corelate the cases. The DNA copy number gain of the LMO1 locus due to duplication was also demonstrated to associate with the cases. These findings suggest that the gene has a role in the development and/or progression of neuroblastoma. It was also reported that LMO3 is a neuroblastoma oncogene. |
| Entity | Apoptosis of the gastric epithelial cells |
| Note | In some gastric-cancer derived cell lines, LMO1 is upregulated by TGFbeta signalling and induces their apoptosis through enhancing GSDMA expression. This TGFbeta-LMO1-GSDMA cascade is considered a mechanism for apoptosis induction in the gastric epithelial cells, and has a role in maintaining their homeostasis. |
 | |
| LMO1 induces apoptosis of the pit cells in TGFbeta signalling. This function is assumed to have a role in homeostasis of the gastric epithelium. | |
| Entity | T-cell acute lymphoblastic leukemia (T-ALL) |
| Disease | Originally, the LMO1 gene was identified at a break point of the translocation t(11;14)(p15;q11), which was frequently observed in T-ALL. Using LMO1 as a probe, LMO2 and LMO3 were identified. LMO1 is expressed in inmature T cells but suppressed in the mature cells, and overexpression of the gene in thymocytes, hematopoeitic progeniter cells located in the thymus, resulted in developing T-ALL in mice. LMO1 acts cooperatively with SCL (Stem cell leukemia) as a transcriptional activator or represser, dependent on the genes and the cells, and enforced expression of LMO1 and SCL in the thymocytes inhibits T-cell differentiation and causes T-ALL. It is known that the LMO1-SCL complex regulates several genes, including suppression of NFKB1 (nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) and PTCRA (pre T-cell antigen receptor alpha), activation of NKX3.1 (NK3 homeobox 1). |
| Bibliography |
| LMO3 interacts with neuronal transcription factor, HEN2, and acts as an oncogene in neuroblastoma. |
| Aoyama M, Ozaki T, Inuzuka H, Tomotsune D, Hirato J, Okamoto Y, Tokita H, Ohira M, Nakagawara A. |
| Cancer Res. 2005 Jun 1;65(11):4587-97. |
| PMID 15930276 |
| The rhombotin family of cysteine-rich LIM-domain oncogenes: distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13. |
| Boehm T, Foroni L, Kaneko Y, Perutz MF, Rabbitts TH. |
| Proc Natl Acad Sci U S A. 1991 May 15;88(10):4367-71. |
| PMID 2034676 |
| Developmentally regulated and tissue specific expression of mRNAs encoding the two alternative forms of the LIM domain oncogene rhombotin: evidence for thymus expression. |
| Boehm T, Spillantini MG, Sofroniew MV, Surani MA, Rabbitts TH. |
| Oncogene. 1991 May;6(5):695-703. |
| PMID 2052354 |
| NFKB1 is a direct target of the TAL1 oncoprotein in human T leukemia cells. |
| Chang PY, Draheim K, Kelliher MA, Miyamoto S. |
| Cancer Res. 2006 Jun 15;66(12):6008-13. |
| PMID 16778171 |
| SCL and LMO1 alter thymocyte differentiation: inhibition of E2A-HEB function and pre-T alpha chain expression. |
| Herblot S, Steff AM, Hugo P, Aplan PD, Hoang T. |
| Nat Immunol. 2000 Aug;1(2):138-44. |
| PMID 11248806 |
| NKX3.1 is a direct TAL1 target gene that mediates proliferation of TAL1-expressing human T cell acute lymphoblastic leukemia. |
| Kusy S, Gerby B, Goardon N, Gault N, Ferri F, Gerard D, Armstrong F, Ballerini P, Cayuela JM, Baruchel A, Pflumio F, Romeo PH. |
| J Exp Med. 2010 Sep 27;207(10):2141-56. Epub 2010 Sep 20. |
| PMID 20855495 |
| Thymic overexpression of Ttg-1 in transgenic mice results in T-cell acute lymphoblastic leukemia/lymphoma. |
| McGuire EA, Rintoul CE, Sclar GM, Korsmeyer SJ. |
| Mol Cell Biol. 1992 Sep;12(9):4186-96. |
| PMID 1508213 |
| TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3. |
| Ono Y, Fukuhara N, Yoshie O. |
| Mol Cell Biol. 1998 Dec;18(12):6939-50. |
| PMID 9819382 |
| GASDERMIN, suppressed frequently in gastric cancer, is a target of LMO1 in TGF-beta-dependent apoptotic signalling. |
| Saeki N, Kim DH, Usui T, Aoyagi K, Tatsuta T, Aoki K, Yanagihara K, Tamura M, Mizushima H, Sakamoto H, Ogawa K, Ohki M, Shiroishi T, Yoshida T, Sasaki H. |
| Oncogene. 2007 Oct 4;26(45):6488-98. Epub 2007 Apr 30. |
| PMID 17471240 |
| The LMO1 and LDB1 proteins interact in human T cell acute leukaemia with the chromosomal translocation t(11;14)(p15;q11). |
| Valge-Archer V, Forster A, Rabbitts TH. |
| Oncogene. 1998 Dec 17;17(24):3199-202. |
| PMID 9872335 |
| Integrative genomics identifies LMO1 as a neuroblastoma oncogene. |
| Wang K, Diskin SJ, Zhang H, Attiyeh EF, Winter C, Hou C, Schnepp RW, Diamond M, Bosse K, Mayes PA, Glessner J, Kim C, Frackelton E, Garris M, Wang Q, Glaberson W, Chiavacci R, Nguyen L, Jagannathan J, Saeki N, Sasaki H, Grant SF, Iolascon A, Mosse YP, Cole KA, Li H, Devoto M, McGrady PW, London WB, Capasso M, Rahman N, Hakonarson H, Maris JM. |
| Nature. 2011 Jan 13;469(7329):216-20. Epub 2010 Dec 1. |
| PMID 21124317 |
| Citation |
| This paper should be referenced as such : |
| Saeki, N ; Sasaki, H |
| LMO1 (LIM domain only 1 (rhombotin 1)) |
| Atlas Genet Cytogenet Oncol Haematol. 2012;16(2):84-86. |
| Free journal version : [ pdf ] [ DOI ] |
| Other Leukemias implicated (Data extracted from papers in the Atlas) [ 8 ] |
| Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ] |
|
Nervous system: Embryonal tumors: Neuroblastoma
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| 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 : Tue Nov 3 09:57:05 CET 2020 |
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