t(9;10)(q34;q22) ZMIZ1/ABL1

2013-12-01   Jean-Loup Huret 

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

Clinics and Pathology

Noted

Only five cases to date have been described with a t(9;10)(q34;q22). Two cases of acute myeloid leukemia (AML) are herein excluded from the study, because they are likely to represent another entity, with perhaps different genes involved. These are two patients aged 44 years (1 female and 1 male), one with a M1-AML, and the other one with a M3-AML and the classical t(15;17)(q22;q21), both with a complex karyotype and no further data (Sato et al., 1995; Schoch et al., 1996).

Disease

B-cell acute lymphoblastic leukemia (B-ALL).

Phenotype stem cell origin

One case was phenotyped as a CD10+ B-ALL.

Epidemiology

Three cases to date, 1 male / 2 female patients, all are paediatric cases so far, one was a 1.5 year old baby (Cooley et al., 2007; Rabin et al., 2008; Soler et al., 2008).

Prognosis

Scarce data, no follow-up; one case was noted as being in complete remission.

Genes Involved and Proteins

Gene name
ABL1 (v-abl Abelson murine leukemia viral oncogene homolog 1)
Location
9q34.12
Protein description
1130-1143 amino acids; ABL1 is composed from N-term to C-term of a CAP, a SRC homology 3 (SH3), SH2 and SH1 tyrosine kinase domains, a conserved PXXP motifs to mediate protein-protein interactions, three nuclear localization signal (NLS) motifs, a DNA-binding domain, a globular (G).actin-binding domain, one nuclear export signal (NES), and a conserved filamentous actin-binding domain. Regulates endocytosis, epithelial-to.mesenchymal transition, cell polarity, adhesion, migration and invasion; in response to cellular stress, including DNA damage, ABL1 induces growth arrest and/or apoptosis (review in Greuber et al., 2013).
Somatic mutations
Apart from the well known role of ABL1 in leukemias, ABL1 has been found overexpressed in a small percentage of breast carcinomas, lung squamous cell carcinomas, and uterine corpus carcinomas.
Gene name
ZMIZ1 (zinc finger MIZ-type containing 1)
Location
10q22.3
Protein description
1067 amino acids (aa). ZMIZ1 is composed from N-term to C-term of a proline-rich region (aa 363-555 (334-555 according to Swiss-Prot)), a nuclear localization signal sequence (aa 691-713), a Miz domain (aa 738-790 (Zn finger 727-804 according to Swiss-Prot)), and a proline-rich region (transcriptional activation domain) (aa 824-1067 ((867-1002 according to Swiss-Prot)). The central region between aa 556 and 790 is the primary binding region for AR (Sharma et al., 2003). Sequence specific DNA binding protein. Transcriptional coactivator related to members of the proteatggactin inhibitor of activated STAT (PIAS) family. Co-activator of AR (androgen receptor). Increases ligand-dependent transcriptional activity of AR, SMAD3, and TP53. ZMIZ1 is able to enhance the sumoylation of AR. ZMIZ1 cooperates with NOTCH1 to regulate the C-MYC pathway. ZMIZ1 is overexpressed in a subset of T-ALL (Rakowski et al., 2013).

Result of the Chromosomal Anomaly

Note

A ZMIZ1/ABL1 hybrid gene was searched for and detected in one case to date (Soler et al., 2003).

Description

5 ZMIZ1-3ABL1. The exon 14 of ZMIZ1 is fused to exon 2 of ABL1.
Atlas Image
t(9;10)(q34;q22) ZMIZ1/ABL1 protein.

Description

197 kDa, 1812 amino acids fusion protein, containing the N-term proline-rich domain of ZMIZ1 and most of ABL1.

Oncogenesis

ZMIZ1/ABL1 may encode a constitutively activated tyrosine kinase.

Bibliography

Pubmed IDLast YearTitleAuthors
175560672007Prognostic significance of cytogenetically detected chromosome 21 anomalies in childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study.Cooley LD et al
238426462013Role of ABL family kinases in cancer: from leukaemia to solid tumours.Greuber EK et al
182539612008Clinical utility of array comparative genomic hybridization for detection of chromosomal abnormalities in pediatric acute lymphoblastic leukemia.Rabin KR et al
231614892013Convergence of the ZMIZ1 and NOTCH1 pathways at C-MYC in acute T lymphoblastic leukemias.Rakowski LA et al
234261362013Ectopic expression of Zmiz1 induces cutaneous squamous cell malignancies in a mouse model of cancer.Rogers LM et al
76329601995TEL and KIP1 define the smallest region of deletions on 12p13 in hematopoietic malignancies.Sato Y et al
87901481996Incidence and implication of additional chromosome aberrations in acute promyelocytic leukaemia with translocation t(15;17)(q22;q21): a report on 50 patients.Schoch C et al
146099562003hZimp10 is an androgen receptor co-activator and forms a complex with SUMO-1 at replication foci.Sharma M et al
180075762008Fusion of ZMIZ1 to ABL1 in a B-cell acute lymphoblastic leukaemia with a t(9;10)(q34;q22.3) translocation.Soler G et al

Summary

Fusion gene

ZMIZ1/ABL1 ZMIZ1 (10q22.3) ABL1 (9q34.12) M|ZMIZ1/ABL1 ZMIZ1 (10q22.3) ABL1 (9q34.12) M t(9;10)(q34;q23)|ZMIZ1/ABL1 ZMIZ1 (10q22.3) ABL1 (9q34.12) TIC

Citation

Jean-Loup Huret

t(9;10)(q34;q22) ZMIZ1/ABL1

Atlas Genet Cytogenet Oncol Haematol. 2013-12-01

Online version: http://atlasgeneticsoncology.org/haematological/1520/t(9;10)(q34;q22)-zmiz1-abl1

External Links