t(3;11)(p25;p15) ANKRD28/NUP98

2011-11-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology

Disease

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML)

Epidemiology

Two cases to date, with a possible identical rearrangement.
A 32-year-old man have had a common acute lymphoblastic leukemia (c-ALL) with a del(9p). A bone marrow transplantation (BMT) was performed. The donor was his sister. Fifteen months later, a secondary AML with erythrophagocytosis developped. The karyotype was 46,XX (suggesting that the leukemic clone derived from the sibling bone marrow donor), with the following anomalies: a t(3;11)(p25;p15), but also the classical t(8;16)(p11;p13) with MYST3/REBBP rearrangement. The patient died a month later. NUP98 was not tested (Schmidt et al., 2004).
A 33-year-old woman with a refractory anemia with excess of blasts in transformation exhibited a t(3;5;11)(p24;q35;p15) with ANKRD28-NUP98 and NUP98-NSD1 rearrangements, Transformation to AML occured 2 weeks later. In spite of a BMT, the patient died 7 months after diagnosis (Ishikawa et al., 2007).

Genes Involved and Proteins

Gene name
ANKRD28 (ankyrin repeat domain 28)
Location
3p25.1
Protein description
1053 and 1086 amino acids isoforms. Contains 30 ankyrin repeats (protein-protein interaction motifs). ANKRD28 forms a complex with BCAR1/p130Cas, CRK, and DOCK1 to enhance BCAR1 phosphorylation. ANKRD28 is required for cell migration (Kiyokawa and Matsuda, 2009). PP6 is a multisubunit enzyme, comprising a catalytic subunit, a phosphatase-associated protein (SAPS) domain regulatory subunit and ankyrin repeat domain subunits. PP6 holoenzyme, comprising PPP6C catalytic, SAPS1-3 regulatory, and ANKRD28 and ANKRD44 subunits, is required for normal mitotic progression (Zeng et al., 2010).
Gene name
NUP98 (nucleoporin 98 kDa)
Location
11p15.4
Protein description
Nucleoporin: associated with the nuclear pore complex. Role in nucleocytoplasmic transport processes.

Result of the Chromosomal Anomaly

Description

Two in-frame fusion transcripts 5 ANKRD28 - 3 NUP98 (exons 18 and 13 respectively), and 5 NUP98 - 3 NSD1 (exons 12 and 7 respectively) were produced in the case reported by Ishikawa et al. in 2007.

Expression localisation

Although 5 NUP98 - 3 partner is the usual fusion transcript involved in leukemogenesis with 11p15 involvement, the present 5 ANKRD28 - 3 NUP98 fusion transcript may have played a role. ANKRD28-NUP98 was localized in the nucleolus and cytoplasm and might have contributed to the leukemogenesis process. Cells transfected with ANKRD28-NUP98 formed more foci than cells transfected with the wild type ANKRD28 (Ishikawa et al., 2007).

Bibliography

Pubmed IDLast YearTitleAuthors
179889902007A novel gene, ANKRD28 on 3p25, is fused with NUP98 on 11p15 in a cryptic 3-way translocation of t(3;5;11)(p25;q35;p15) in an adult patient with myelodysplastic syndrome/acute myelogenous leukemia.Ishikawa M et al
194584772009Regulation of focal adhesion and cell migration by ANKRD28-DOCK180 interaction.Kiyokawa E et al
150851632004RT-PCR and FISH analysis of acute myeloid leukemia with t(8;16)(p11;p13) and chimeric MOZ and CBP transcripts: breakpoint cluster region and clinical implications.Schmidt HH et al
211873292010Protein phosphatase 6 regulates mitotic spindle formation by controlling the T-loop phosphorylation state of Aurora A bound to its activator TPX2.Zeng K et al

Summary

Fusion gene

ANKRD28/NUP98 ANKRD28 (3p25.1) NUP98 (11p15.4) M|ANKRD28/NUP98 ANKRD28 (3p25.1) NUP98 (11p15.4) M t(3;5;11)(p25;q35;p15)|ANKRD28/NUP98 ANKRD28 (3p25.1) NUP98 (11p15.4) TIC

Citation

Jean-Loup Huret

t(3;11)(p25;p15) ANKRD28/NUP98

Atlas Genet Cytogenet Oncol Haematol. 2011-11-01

Online version: http://atlasgeneticsoncology.org/haematological/1509/t(3;11)(p25;p15)

External Links