|Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France. email@example.com|
|Abstract||Review on t(2;2)(p22;p22) and del(2)(p22p22) LTBP1/BIRC6 in acute myeloid leukemia, with data on the genes involved.|
|Keywords||chromosome 2; t(2;2)(p22;p22); LTBP1; BIRC6; acute myeloid leukemia|
|ICD-Morpho||9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS|
|Clinics and Pathology|
|Note||Only two cases to date of t(2;2)(p22;p22) or del(2)(p22p22) LTBP1/BIRC6 in acute myeloid leukemia have been described (Cancer Genome Atlas Research Network 2013; Yoshihara et al. 2015). This chromosomes and genes rearrangements have also been found in a case of breast carcinoma, and in a case of lung squamous cell carcinoma: t(2;2)(p22;p22) or del(2)(p22p22) LTBP1/BIRC6 in solid tumors.|
|Disease||Acute myeloid leukemia|
|Epidemiology||Data were described in only one case: a 75-year old male patient presented with AML-M2. Overall survival was 0.1 month (Cancer Genome Atlas Research Network 2013).|
|Cytogenetics||The karyotype was normal (cryptic rearrangement).|
|Genes involved and Proteins|
|Note||FLT3 mutation was positive; IDH1 R132, R140, R172 were negative; activating RAS was negative; NPMc was negative.|
|Protein|| BIRC6 contains two domains: a N-terminal BIR repeat (needed for interactions with caspases and IAP-binding motif (IBM) containing proteins) and a C-terminal UBC domain (which can form a thiolester linkage with ubiquitin transferred by E1).|
Inhibitor of apoptosis: BIRC6 is a peripheral membrane protein of the trans-Golgi network that protects cells from apoptosis
BIRC6 and treatment resistance: Silencing of BIRC6 has been shown to sensitize cancer cells to various anticancer agents
BIRC6 is essential in embryonic development.
Regulator of cytokinesis: BIRC6 is a major regulator of abscission, the final stage of cytokinesis.
Regulator of mitosis: BIRC6 interacts with CCNA2 (cyclin A) and promotes its degradation in early mitosis
BIRC6 and autophagy: BIRC6 is required to inhibit autophagy
(Iris Luk and Wang, 2014).
BIRC6 is involved in myelodysplastic syndromes and acute myeloid leukemias, colorectal cancer, neuroblastoma, skin melanoma, non-small cell lung cancer, prostate cancer, ovarian cancer, hepatocellular carcinoma and breast cancer.
|Dna / Rna||Eleven splice variants.|
|Protein|| 1721 amino acids; belongs to the LTBP/fibrillin family. |
LTBP1 is composed of a signal peptide: (amino acids 1-23), 18 epidermal growth factor (EGF)-like repeats and four cysteines rich domains, the TB (TGFb binding protein-like) domains. The LTBP1 C-terminus interacts with the extracellular matrix via fibrillin microfibrils. EGF-like repeats provide stability to the protein structure
TGFB1 is secreted as a biologically latent complex composed of LTBP1, a latency associated peptide (LAP), (LAP is the TGFB1 pro-peptide which regulates latency, that is cleaved intracellularly prior to secretion), and the TGFB1 cytokine. LTBP1 plays roles in facilitating the folding and secretion of TGFB1 from the cell, and activation.
LTBP1 interacts with FBN1 (fibrillin 1). This interaction allows LTBP1 to sequester TGFB1 to fibrillin microfibrils; EFEMP2 (EGF containing fibulin-like extracellular matrix protein 2, or fibulin4) and ADAMTSL proteins form ternary complexes with LTBP1 and fibrillin.
LTBP1 is involved in epithelial-mesenchymal interaction and epithelial differentiation (Mazzieri et al., 2005; Robertson et al., 2014).
|Result of the chromosomal anomaly|
|Description||5' LTBP1 - 3' BIRC6|
|To be noted|
| Additional cases are needed to delineate the epidemiology of this rare entity: |
you are welcome to submit a paper to our new Case Report section.
|Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia.|
|Cancer Genome Atlas Research Network.|
|N Engl J Med. 2013 May 30;368(22):2059-74. doi: 10.1056/NEJMoa1301689. Epub 2013 May 1.|
|BIRC6 (Baculoviral IAP repeat-containing 6);|
|Jentsch, S ; Pohl, C.|
|Atlas Genet Cytogenet Oncol Haematol. http://atlasgeneticsoncology.org/Genes/BIRC6ID798ch2p22.html|
|Expression of truncated latent TGF-beta-binding protein modulates TGF-beta signaling.|
|Mazzieri R, Jurukovski V, Obata H, Sung J, Platt A, Annes E, Karaman-Jurukovska N, Gleizes PE, Rifkin DB.|
|J Cell Sci. 2005 May 15;118(Pt 10):2177-87.|
|NMR spectroscopic and bioinformatic analyses of the LTBP1 C-terminus reveal a highly dynamic domain organisation.|
|Robertson IB, Handford PA, Redfield C.|
|PLoS One. 2014 Jan 29;9(1):e87125. doi: 10.1371/journal.pone.0087125.|
|The landscape and therapeutic relevance of cancer-associated transcript fusions.|
|Yoshihara K, Wang Q, Torres-Garcia W, Zheng S, Vegesna R, Kim H, Verhaak RG.|
|Oncogene. 2015 Sep 10;34(37):4845-54. doi: 10.1038/onc.2014.406. Epub 2014 Dec 15.|
|This paper should be referenced as such :|
|t(2;2)(p22;p22) LTBP1/BIRC6; del(2)(p22p22) LTBP1/BIRC6;|
|Atlas Genet Cytogenet Oncol Haematol. in press|
|On line version : http://AtlasGeneticsOncology.org/Anomalies/t0202p22p22ID1714.html|
|Translocations implicated (Data extracted from papers in the Atlas)|
|Mitelman database||t(2;2)(p22;p22) [Case List] t(2;2)(p22;p22) [Association List] Mitelman database (CGAP - NCBI)|
|arrayMap||Morph ( 9861/3) - arrayMap (UZH-SIB Zurich) [auto + random 100 samples .. if exist ] [tabulated segments]|
|Disease database||t(2;2)(p22;p22) LTBP1/BIRC6|
|REVIEW articles||automatic search in PubMed|
|Last year articles||automatic search in PubMed|
|All articles||automatic search in PubMed|
|© Atlas of Genetics and Cytogenetics in Oncology and Haematology||indexed on : Fri Jun 30 11:22:50 CEST 2017|
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