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t(11;16)(q23;q24) KMT2A/USP10

Written2018-12Elena Zerkalenkova, Svetlana Lebedeva, Anna Kazakova, Pavel Baryshev, Claus Meyer, Rolf Marschalek, Galina Novichkova, Michael Maschan, Aleksey Maschan, Yulia Olshanskaya
Dmitry Rogachev Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Samora Mashela str., 1, Moscow, 117997, Russia (EZ, AK, PB, GN, MM, AM, YuO), Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow, 119991, Russia (SL), Goethe-University of Frankfurt, Diagnostic Center of Acute Leukemia, Biocenter, Max-von-Laue-Str., 9, D-60438, Frankfurt / Main, Germany (CM, RM) / eazerkalenkova@gmail.com

Abstract Review on t(11;16)(q23;q24), with data on clinics, and the genes involved.

Keywords Chromosome 11; Chromosome 16; KMT2A; USP10; Acute monoblastic leukaemia

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424
ICD-Morpho 9891/3 Acute monoblastic and monocytic leukaemia
Atlas_Id 1802
 
  Partial karyogram representing the t(11;16)(q23;q24) (Zerkalenkova et al., 2018).

Clinics and Pathology

Disease Acute monoblastic leukaemia (AML-M5a)
Epidemiology Poorly defined, only one case described to date, a 15 years-old boy with AML-M5a relapse (Zerkalenkova et al., 2018).
Treatment The patient was treated according to AML-BFM-2004 protocol and remission was achieved after the 2nd induction course. After two years a bone marrow relapse of AML M5a was diagnosed.
Prognosis The prognosis was poor, the current patient died due to the progression of the disease (Zerkalenkova et al., 2018).

Cytogenetics

 
  The probe was hybridized to metaphase and displayed 3'-portion of KMT2A translocated to chromosome 16 (Zerkalenkova et al., 2018).
Probes MLL dual color break apart rearrangement probe.
Additional anomalies del(7p)

Genes involved and Proteins

Gene NameKMT2A (lysine (K)-specific methyltransferase 2A)
Location 11q23.3
Dna / Rna KMT2A gene consists of 37 exons encoding a 3969 amino-acid nuclear protein with a molecular weight of nearly 431 kDa.
Protein 431 kDa; contains two DNA binding motifs (a AT hook and Zinc fingers), and a DNA methyl transferase motif; wide expression; nuclear localization; transcriptional regulatory factor.
Gene NameUSP10 (ubiquitin specific peptidase 10)
Location 16q24.1
Dna / Rna USP10 gene consists of 14 exons encoding a 798 amino-acid protein with a molecular weight of 87134 Da.
Protein 87134 Da; belongs to the ubiquitin-specific proteases family; contains N-terminal thiol hydrolase catalytic domain and C-terminal Ataxin-2 extension that mediates protein-protein interactions; widely expressed; found in nucleus, cytoplasm and early endosomes; deubiquitinates various substrates. Main substrate: TP53. Upon DNA damage USP10 moves to nucleus where deubiquitinates the p53 protein thus increasing p53 levels (Yuan et al., 2010).

Result of the chromosomal anomaly

Hybrid gene
Note KMT2A/USP10 fusion gene was detected by LDI-PCR (Zerkalenkova et al., 2018).
  Upper line: KMT2A/USP10 fusion gene sequence. Lower line: KMT2A/USP10 fusion transcript RT-PCR and Sanger sequencing.
 
Description KMT2A/USP10 fusion gene contains 5'-portion of KMT2A and 3'-portion of USP10. Breakpoints are localized in KMT2A intron 12 and USP10 intron 1.
  
Fusion Protein
Description KMT2A/USP10 fusion protein joins amino-acid residue 1493 of KMT2A to amino-acid residue 8 of USP10 thus retaining KMT2A AT hooks, Pro-rich, and the Zn finger CXXC type domains and almost entire USP10.
  

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.

Bibliography

USP10 regulates p53 localization and stability by deubiquitinating p53.
Yuan J, Luo K, Zhang L, Cheville JC, Lou Z.
Cell. 2010 Feb 5;140(3):384-96. doi: 10.1016/j.cell.2009.12.032. Epub 2010 Jan 21.
PMID 20096447
 
A case of pediatric acute myeloid leukemia with t(11;16)(q23;q24) leading to a novel KMT2A-USP10 fusion gene.
Zerkalenkova E, Lebedeva S, Kazakova A, Baryshev P, Meyer C, Marschalek R, Novichkova G, Maschan M, Maschan A, Olshanskaya Y.
Genes Chromosomes Cancer. 2018 Oct;57(10):522-524. doi: 10.1002/gcc.22646. Epub 2018 Aug 14.
PMID 30107050
 

Citation

This paper should be referenced as such :
Zerkalenkova E, Lebedeva S, Kazakova A, Baryshev P, Meyer C, Marschalek R, Novichkova G, Maschan M, Maschan A, Olshanskaya Y
t(11;16)(q23;q24) KMT2A/USP10;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Anomalies/t1116q23q24KMT2A-USP10ID1802.html


Translocations implicated (Data extracted from papers in the Atlas)

 t(11;16)(q23;q24) KMT2A/USP10

External links

Mitelman databaset(11;16)(q23;q24) [Case List]    t(11;16)(q23;q24) [Transloc-MCList] KMT2A/USP10 [Fusion-MCList]
arrayMap (UZH-SIB Zurich)Morph ( 9891/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
 
 
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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indexed on : Fri Jan 11 13:05:23 CET 2019


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