Atlas of Genetics and Cytogenetics in Oncology and Haematology

OPEN ACCESS JOURNAL INIST-CNRS

Gene Section Short Communication

NOL4L (nucleolar 4 like) Jean Loup Huret [email protected]

Published in Atlas Database: October 2018 Online updated version : http://AtlasGeneticsOncology.org/Genes/NOL4LID51676ch20q11.html Printable original version : http://documents.irevues.inist.fr/bitstream/handle/2042/70456/10-2018-NOL4LID51676ch20q11.pdf DOI: 10.4267/2042/70456 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2019 Atlas of Genetics and Cytogenetics in Oncology and Haematology

Abstract Transcription Review on NOL4L, with data on DNA, on the 8 potential splice forms coding for potential protein encoded, and where the is implicated. with 76 amino acids (aa) to 680 aa. Keywords Protein NOL4L; C20orf112; C20orf113; Acute lymphoblastic leukemia; Acute myeloid leukemia: Note Breast adenocarcinoma; Skin melanoma; Uterus Nothing is known concerning the domains of the cancer; Bladder cancer. protein, nor it's function. Identity Description Two coding proteins: NOL4L-010, from: 11 exons; Other names: LOC140688 transcript length: 6,577 bps translation: 680 amino HGNC (Hugo): NOL4L acids; and NOL4L-001, from: 8 exons; transcript length: 5,991 bps translation: 436 amino acids. A Location: 20q11.2 Poly-Asp is found at aa 161 to 169 according to Vega Local order (http://vega.archive.ensembl.org/Homo_sapiens/Ge Cen --- PLAGL2, POFUT1, KIF3B, ASXL1, ne/Summary?db=core;g=OTTHUMG00000032219 NOL4L, NOL4L-DT, C20orf203, COMMD7, ;r=20:32443059-32585074) and UniProt DNMT3B ---Tel (https://www.uniprot.org/uniprot/Q96MY1#express Note ion). This gene and protein is very poorly known; a very Expression few data comes from the literature, and other data Expressed in all tissues; High expression in the from databases. testis, and, to a lesser extend, in the small DNA/RNA intestine,other digestive organs, brain and bone marrow. NOL4L orthologs are present in most Description vertebrates and are well conserved. 11 exons

Atlas Genet Cytogenet Oncol Haematol. 2019; 23(6) 143 NOL4L (nucleolar protein 4 like) Huret JL

In zebrafish embryos, Znol4lb (the zebrafish nol4l - fusion/translocation t(17;20)(q22;q11) with the highest identity with human NOL4L) MMD/NOL4L in breast adenocarcinoma (Yoshihara mRNA is localized to the intermediate mesoderm. It et al. 2015). is expressed in the central nervous system, - fusion 20q11-20q11 NOL4L/ COMMD7 in breast pronephros, the gut and, at low levels, in the adenocarcinoma (Yoshihara et al. 2015). hematopoietic cells (Borah et al. 2016). - fusion 20q11-20q11 NOL4L/ EFCAB8 in Localisation malignant melanoma of the skin (Hu et al., 2018). - fusion 20q11-20q11 PDRG1/NOL4L in malignant Mainly localized to the nucleoplasm. epithelial tumor of the uterus corpus (Hu et al., Function 2018). Acccording to BioGRID Pediatric acute lymphoblastic (https://thebiogrid.org/12665), interacts with: leukemia (ALL) CTBP1 (C-terminal binding protein 1), corepressor Note targeting various transcription regulators. 5 cases of dic(9;20) (p13;q11) PAX5/NOL4L TEX9 (testis expressed 9). available to date (Nebral et al., 2007; An et al., 2008; SRPK1 (SRSF protein kinase 1), involved in the Kawamata et al., 2008; Kawamata et al. 2012). regulation of splicing via phosphorylation of splicing factors. Hybrid/Mutated gene CTBP2 (C-terminal binding protein 2), corepressor In one case, exon 5 of PAX5 was fused to exon 8 of targeting various transcription regulators. NOL4L, and in four cases, exon 8 of PAX5 was SKA3 (spindle and kinetochore associated complex fused to exon 3 of NOL4L, producing two proteins, subunit 3), component of a microtubule-binding a short (PAX5/C20ORF112S) and long complex essential for segregation. (PAX5/C20ORF112L) form, localizing in the TRIM25 (tripartite motif containing 25), ubiquitin nucleus, and/or in the cytoplasm and the nucleus E3 ligase. (Kawamata et al., 2008). MIR206 (microRNA 206). Oncogenesis Four downstream target of PAX5 ( ATP1B1, Implicated in BLK, SEPT2 and TCF7L2) were down-regulated by Top note induction of PAX5/NOL4L. Loss of the C-terminal end of PAX5 may play role in generation of a Expression level according to dominant negative form of mutated PAX5 (https://www.ncbi.nlm.nih.gov/gene/140688) and (Kawamata et al., 2008). The Human Protein Atlas (http://www.proteinatlas.org/ENSG00000197183- Acute myeloid leukemia (AML) NOL4L/pathology): Note High expression of NOL4L is an unfavourable A 62-year-old man was diagnosed with AML with prognostic factor in endometrial cancer. maturation (M2- AML), and presented with a High expression of NOL4L is a favourable t(20;21)(q11.2;q22.1) RUNX1/NOL4L prognostic factor in urothelial cancer. accompanied with monosomy 7 (Guastadisegni et al. Expression level of NOL4L has no prognostic 2010). significance in: Glioma, Thyroid cancer, Lung cancer, Liver cancer, Pancreatic cancer, Head and Hybrid/Mutated gene neck cancer, Stomach cancer, Colorectal cancer, RUNX1 exon 6 was fused to NOL4L exon 8. Renal cancer, Prostate cancer, Testis cancer, Breast Oncogenesis cancer, Cervical cancer, Ovarian cancer, Melanoma. Wild-type NOL4L was expressed at low levels in Main translocations: (detailed herein below) AML and normal bone marrow, whereas the - dic(9;20)(p13;q11) PAX5/NOL4L. RUNX1/NOL4L was expressed at high levels - t(20;21)(q11;q22) RUNX1/NOL4L. (Guastadisegni et al. 2010). Other fusion transcripts: (data extracted from the Atlas References http://atlasgeneticsoncology.org//Bands/20q11.html An Q, Wright SL, Konn ZJ, Matheson E, Minto L, Moorman ) AV, Parker H, Griffiths M, Ross FM, Davies T, Hall AG, - fusion/translocation t(7;20)(p22;q11) Harrison CJ, Irving JA, Strefford JC. Variable breakpoints ACTB/NOL4L in triple-negative (TN) target PAX5 in patients with dicentric : a adenocarcinoma. The triple-negative breast cancer model for the basis of unbalanced translocations in cancer. subtype is the most aggressive form of invasive Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):17050-4 breast adenocarcinoma (Asmann et al. 2012). Asmann YW, Necela BM, Kalari KR, Hossain A, Baker TR, Carr JM, Davis C, Getz JE, Hostetter G, Li X, McLaughlin SA, Radisky DC, Schroth GP, Cunliffe HE, Perez EA,

Atlas Genet Cytogenet Oncol Haematol. 2019; 23(6) 144

NOL4L (nucleolar protein 4 like) Huret JL

Thompson EA. Detection of redundant fusion transcripts as Y, Koehler R, Flohr T, Miller CW, Harbott J, Ludwig WD, biomarkers or disease-specific therapeutic targets in breast Stanulla M, Schrappe M, Bartram CR, Koeffler HP. Cloning cancer. Cancer Res. 2012 Apr 15;72(8):1921-8 of genes involved in chromosomal translocations by high- resolution single nucleotide polymorphism genomic Borah S, Barrodia P, Swain RK. Nucleolar protein 4-like has microarray Proc Natl Acad Sci U S A 2008 Aug a complex expression pattern in zebrafish embryos. Int J 19;105(33):11921-6 Dev Biol. 2016;60(1-3):53-6 Nebral K, König M, Harder L, Siebert R, Haas OA, Strehl S. Guastadisegni MC, Lonoce A, Impera L, Di Terlizzi F, Identification of PML as novel PAX5 fusion partner in Fugazza G, Aliano S, Grasso R, Cluzeau T, Raynaud S, childhood acute lymphoblastic leukaemia Br J Haematol Rocchi M, Storlazzi CT. CBFA2T2 and C20orf112: two 2007 Oct;139(2):269-74 novel fusion partners of RUNX1 in acute myeloid leukemia. Leukemia. 2010 Aug;24(8):1516-9 Yoshihara K, Wang Q, Torres-Garcia W, Zheng S, Vegesna R, Kim H, Verhaak RG. The landscape and therapeutic Hu X, Wang Q, Tang M, Barthel F, Amin S, Yoshihara K, relevance of cancer-associated transcript fusions Lang FM, Martinez-Ledesma E, Lee SH, Zheng S, Verhaak Oncogene 2015 Sep 10;34(37):4845-54 RGW. TumorFusions: an integrative resource for cancer- associated transcript fusions Nucleic Acids Res 2018 Jan This article should be referenced as such: 4;46(D1):D1144-D1149 Huret JL. NOL4L (nucleolar protein 4 like). Atlas Genet Kawamata N, Ogawa S, Zimmermann M, Niebuhr B, Cytogenet Oncol Haematol. 2019; 23(6):143-145. Stocking C, Sanada M, Hemminki K, Yamatomo G, Nannya

Atlas Genet Cytogenet Oncol Haematol. 2019; 23(6) 145