| Written | 2003-12 | Jacques Boyer |
| Laboratoire d' hématologie, CH du MANS, France |
| Identity |
| ICD-Topo | C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS |
| ICD-Morpho | 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS |
| Atlas_Id | 1189 |
| Note | Two distinct clinical syndromes have been associated with the 8p11-12 region : The partners of 8p11 are 8q13, 14q11, 16p13, 19q13, 22q13 and 3q27, 17q12 in a complexe translocation t(3;8;17)(q27;p11; q12). |
| Clinics and Pathology |
| Disease | |
| Epidemiology | Rare. Young age (6 patients, median : 23.5 years) and female sexe. |
| Cytology | Morphology feature observed in AML with t(8;16). |
| Prognosis | Probably poor. |
| Cytogenetics |
| Cytogenetics Morphological | Inv(8) (p11q13) is a variant of t(8;16) (p11;p13) |
| Additional anomalies | In one case der(10)t(1;10)(q25;p15) |
| Genes involved and Proteins |
| Gene Name | KAT6A (MYST histone acetyltransferase (monocytic leukemia) 3 |
| Location | 8p11.21 |
| Note | MOZ contains a LAP (Leukemia associated protein) zinc finger domain , a HAT domain (Histone acetyltransferase) and a acidic domain. Detection by FISH : YAC 176C9. |
| Protein | ZNF220 Monocytic leukemia zinc finger protein. 2004 amino acids and 225 kDa nuclear protein, with 2 LAP/PHD-type zinc fingers. MOZ is a histone acetyltransferase (HAT) and the founding member of the MYST family of HATs, a family that includes proteins involved in cell cycle regulation, chromatin remodeling and dosage compensation. MOZ plays an important role during hematopoiesis with his transcriptional coregulator activity. |
| Gene Name | NCOA2 (nuclear receptor coactivator 2) |
| Location | 8q13.3 |
| Note | Aliases : GRIP1, NCoA-2. Nuclear receptors are ligand-inductible transcription factors with three structural domains : an activation function AF-1, a DNA-binding domain and a second activation function AF-2 that is mediated by nuclear coactivators (NRCoAs) : TIF2 was recently shown to be one such mediators of AF-2 function. Detection by FISH : PAC clone 192D10 |
| Protein | The TIF-2 protein is homologous to other NRCoAs specically SRC-1 (alias NcoA-1). This protein have HAT activity and also interacts directly with CBP. It is likely that TIF-2 mediates transcriptional activation by a mechanism involving chromatin remodeling. |
| Result of the chromosomal anomaly |
| Description | The fusion gene produces a mRNA containing the 5¹ end of MOZ appended in translational frame to the 3¹ end of TIF2. The inv(8) MOZ breakpoint is distinct from the breakpoint in the MOZ -CBP fusion. The fusion product retains the zinc fingers, the HAT domain of MOZ along with the HAT domains and CBP interacting domain of TIF2. |
| Description | MOZ-TIF2 |
| Oncogenesis | The ability of HATs to affect the chromatin structure and regulate gene expression is well appreciated. How the MOZ-TIF2 fusion protein is involved in acute leukemia is not known, but it probably affects the chromatin condensation. It may modulate or augment the transcriptional activity of genes normaly regulated by MOZ or it may serve as a bridge between MOZ and CBP. Recently, it was demonstrated that MOZ-TIF2 has transforming properties in vitro and causes AML. The C2HC nucleosome recognition motif of MOZ and MOZ-TIF2 interaction with CBP are essential for transformation. |
| 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. | |
| Case Report | inv(8)(p11.2q13) found in a patient with chronic myelomonocytic leukemia that progressed to acute myeloid leukemia |
| Bibliography |
| Abnormalities of chromosome band 8p11 in leukemia: two clinical syndromes can be distinguished on the basis of MOZ involvement. |
| Aguiar RC, Chase A, Coulthard S, Macdonald DH, Carapeti M, Reiter A, Sohal J, Lennard A, Goldman JM, Cross NC |
| Blood. 1997 ; 90 (8) : 3130-3135. |
| PMID 9376594 |
| A novel fusion between MOZ and the nuclear receptor coactivator TIF2 in acute myeloid leukemia. |
| Carapeti M, Aguiar RC, Goldman JM, Cross NC |
| Blood. 1998 ; 91 (9) : 3127-3133. |
| PMID 9558366 |
| MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome binding motif and TIF2-mediated recruitment of CBP. |
| Deguchi K, Ayton PM, Carapeti M, Kutok JL, Snyder CS, Williams IR, Cross NC, Glass CK, Cleary ML, Gilliland DG |
| Cancer cell. 2003 ; 3 (3) : 259-271. |
| PMID 12676584 |
| A new specific chromosomal rearrangement, t(8;16) (p11;p13), in acute monocytic leukaemia. |
| Heim S, Avanzi GC, Billström R, Kristoffersson U, Mandahl N, Bekassy AN, Garwicz S, Wiebe T, Pegoraro L, Falda M |
| British journal of haematology. 1987 ; 66 (3) : 323-326. |
| PMID 3476150 |
| Three cases of translocation (8;16)(p11;p13) observed in acute myelomonocytic leukemia: a new specific subgroup? |
| Laï JL, Zandecki M, Jouet JP, Savary JB, Lambiliotte A, Bauters F, Cosson A, Deminatti M |
| Cancer genetics and cytogenetics. 1987 ; 27 (1) : 101-109. |
| PMID 3472640 |
| [FGFR1 and MOZ, two key genes involved in malignant hemopathies linked to rearrangements within the chromosomal region 8p11-12] |
| Pébusque MJ, Chaffanet M, Popovici C, Birnbaum D |
| Bulletin du cancer. 2000 ; 87 (12) : 887-894. |
| PMID 11174118 |
| Citation |
| This paper should be referenced as such : |
| Boyer, J |
| inv(8)(p11q13) |
| Atlas Genet Cytogenet Oncol Haematol. 2004;8(2):83-84. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Anomalies/inv8p11q13ID1189.html |
| Other genes implicated (Data extracted from papers in the Atlas) [ 2 ] |
| Genes | KAT6A | EP300 |
| Translocations implicated (Data extracted from papers in the Atlas) |
| inv(8)(p11q13) KAT6A/NCOA2 | |
| External links |
| Mitelman database | inv(8)(p11q13) [Case List] inv(8)(p11q13) [Transloc-MCList] KAT6A/NCOA2 [Fusion-MCList] |
| arrayMap (UZH-SIB Zurich) | Topo ( C42) Morph ( 9861/3) - [auto + random 100 samples .. if exist ] [tabulated segments] |
| Mitelman database | KAT6A/NCOA2 [MCList] KAT6A (8p11.21) NCOA2 (8q13.3) |
| TICdb | KAT6A/NCOA2 KAT6A (8p11.21) NCOA2 (8q13.3) |
| 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 : Mon May 11 15:50:40 CEST 2020 |
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