t(3;11)(q13.13;q23) KMT2A/KIAA1524

2012-05-01   C Michel Zwaan  , Marry M van den Heuvel-Eibrink  , H Berna Beverloo  , Rolf Marschalek  , Claus Meyer  , Eva A Coenen  

1.Department of pediatric oncology, Erasmus Medical Center / Sophia Children s hospital, Rotterdam, the Netherlands (EAC, CMZ, MMHE); Department of clinical genetics, Erasmus Medical Center / Sophia Children s hospital, Rotterdam, the Netherlands (HBB); Institute of pharmaceutical biology, ZAFES, Diagnostic center of acute leukemias (DCAL), Frankfurt, Germany (RM, CM)
2.Department of pediatric oncology, Erasmus Medical Center / Sophia Childrens hospital, Rotterdam, the Netherlands (EAC, CMZ, MMHE); Department of clinical genetics, Erasmus Medical Center / Sophia Childrens hospital, Rotterdam, the Netherlands (HBB); Institute of pharmaceutical biology, ZAFES, Diagnostic center of acute leukemias (DCAL), Frankfurt, Germany (RM, CM)

Clinics and Pathology

Disease

M5 acute myeloid leukemia (AML)

Clinics

Poorly known: one case, a 4-months old girl with 46,XX,t(3;11)(q12~13;q23).

Genes Involved and Proteins

Gene name
KMT2A (myeloid/lymphoid or mixed lineage leukemia)
Location
11q23.3
Dna rna description
21 exons, spanning about 100 kb; 13-17 kb mRNA.
Protein description
431 kDa; contains two DNA binding motifs (an AT hook and Zinc fingers), a DNA methyl transferase motif, a bromodomain; transcriptional regulatory factor; nuclear localisation.
Gene name
KIAA1524
Location
3q13.13
Note
Alias: CIP2A.
Dna rna description
21 exons, spanning about 40 kb; 3-4 kb mRNA.
Protein description
905 amino acids containing protein with transmembrane domain and coiled coil domain; inhibits MYC directed inhibitory function of protein phosphatase 2A (PP2A).

Result of the Chromosomal Anomaly

Atlas Image
A. DNA sequence as derived from a Long distance inverse-PCR experiment. Shown in black is the sequence from MLL intron 9, exon 10 (Bold) and intron 10 respectively, in blue two inserted nucleotides, in red the sequence from KIAA1524 intron 16, exon 17 (Bold) and intron 17 respectively. (figure adapted from reference). B. Transcript (figure adapted from reference).

Description

In the described patient MLL exon 1-10 are fused to KIAA1524 exon 17-21 due to translocation between MLL intron 10 and KIAA1524 intron 16.

Transcript

See figure above.

Detection protocole

RT-PCR according to reference.
Atlas Image
MLL-KIAA1524 fusion protein is shown and its wildtype predecessors. AT: AT-hook, SNL1 and SNL2: subnuclear localization sites, MT: methyltransferase, PHD1-3 and PHD4: plant homology domains, BD: binding domain, FYRC and FYRN: domains involved in heterodimerisation, TASPASE1: taspase 1 cleavage sites, TAD: transcriptional activation domain, SET: Su(var)3-9, enchancer-of-zeste trithorax domain, CC: coiled coil domain, TMD: transmembrane domain, aa: amino acids. (figure adapted from reference).

Description

From the fusion in the described patient a fusion protein of 1673 amino acids is expected.

Expression localisation

Unknown.

Article Bibliography

Pubmed IDLast YearTitleAuthors
209432692011KIAA1524: A novel MLL translocation partner in acute myeloid leukemia.Coenen EA et al

Summary

Fusion gene

KMT2A/KIAA1524 KMT2A (11q23.3) KIAA1524 (3q13.13) COF 1833 1834|KMT2A/KIAA1524 KMT2A (11q23.3) KIAA1524 (3q13.13) TIC

Citation

C Michel Zwaan ; Marry M van den Heuvel-Eibrink ; H Berna Beverloo ; Rolf Marschalek ; Claus Meyer ; Eva A Coenen

t(3;11)(q13.13;q23) KMT2A/KIAA1524

Atlas Genet Cytogenet Oncol Haematol. 2012-05-01

Online version: http://atlasgeneticsoncology.org/haematological/1593/t(3;11)(q13-13;q23)-kmt2a-kiaa1524