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

2018-12-01   Svetlana Lebedeva , Anna Kazakova , Pavel Baryshev , Claus Meyer , Rolf Marschalek , Galina Novichkova , Michael Maschan , Aleksey Maschan , Yulia Olshanskaya , Elena Zerkalenkova 

1.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.

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

Atlas Image
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 name
KMT2A (lysine (K)-specific methyltransferase 2A)
Location
11q23.3
Dna rna description
KMT2A gene consists of 37 exons encoding a 3969 amino-acid nuclear protein with a molecular weight of nearly 431 kDa.
Protein description
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 name
USP10 (ubiquitin specific peptidase 10)
Location
16q24.1
Dna rna description
USP10 gene consists of 14 exons encoding a 798 amino-acid protein with a molecular weight of 87134 Da.
Protein description
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

Note

KMT2A/USP10 fusion gene was detected by LDI-PCR (Zerkalenkova et al., 2018).
Atlas Image
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.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.

Highly cited references

Pubmed IDYearTitleCitations
301070502018A case of pediatric acute myeloid leukemia with t(11;16)(q23;q24) leading to a novel KMT2A-USP10 fusion gene.5

Bibliography

Pubmed IDLast YearTitleAuthors
200964472010USP10 regulates p53 localization and stability by deubiquitinating p53.Yuan J et al
301070502018A case of pediatric acute myeloid leukemia with t(11;16)(q23;q24) leading to a novel KMT2A-USP10 fusion gene.Zerkalenkova E et al

Summary

Fusion gene

KMT2A/USP10
Atlas Image
Partial karyogram representing the t(11;16)(q23;q24) (Zerkalenkova et al., 2018).

Citation

Svetlana Lebedeva ; Anna Kazakova ; Pavel Baryshev ; Claus Meyer ; Rolf Marschalek ; Galina Novichkova ; Michael Maschan ; Aleksey Maschan ; Yulia Olshanskaya ; Elena Zerkalenkova

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

Atlas Genet Cytogenet Oncol Haematol. 2018-12-01

Online version: http://atlasgeneticsoncology.org/haematological/1802/t(11;16)(q23;q24)