t(10;10)(p12;q21) CTNNA3/ARHGAP21

2018-08-01   Jean-Loup Huret 



Review on t(10;10)(p12;q21) , with data on clinics and the genes involved

Clinics and Pathology


Only one case to date, a 7-year old boy (Zhang et al. 2012).


Outcome: relapse with lineage switch at 13 months after diagnosis; the patient died at 25 months post diagnosis.

Genes Involved and Proteins

To be noted, a missense mutation in DCLRE1C
Gene name
Dna rna description
The transcript has 26 exons.
Protein description
1958 amino acids (aa). ARHGAP21 acts as a Rho GTPase-activating protein for RHOA, RHOC and CDC42, ARHGAP21 plays a role in cell proliferation, migration, vesicle traffic, cell adhesions and insulin secretion. ARHGAP21 is implicated in many tumor tissues (Ferreira Pissarra et al. 2016).
Gene name
Dna rna description
The transcript has 18 exons.
Protein description
895 aa for the longest isoform. CTNNA3 is an α-catenin. CTNNA3 plays a role in cell-cell adhesion: catenins link the single-pass type I transmembrane linker proteins cadherins (cell-cell adhesion molecule expressed in adherents junctions) to the actin filament network. α-catenins bind the cytoplasmic domains of cadherins through β-catenin to actin filaments.
Protein description
An heterozygous constitutional (germline) deletion of CTNNA3 was found in a hybrid neurofibroma/ schwannoma of a patient with clinically diagnosed neurofibromatosis type 2. Loss of CTNNA3 protein expression was found in neurofibromas, schwannomas, and malignant peripheral nerve sheath tumors. Depletion of CTNNA3 in Schwann cells was associated with reduced RNA of CDH1 (E-cadherin) via induction of SNA1, SNAI2 (E-cadherin repressors) as well as disaggregation of the actin cytoskeleton and epithelial-mesenchymal transition promotion
Protein description
CTNNA3, is a tumor suppressor in hepatocellular carcinoma, inhibiting the proliferation, migration an d invasion. CTNNA3 inhibited AKT signal, and in turn decreased PCNA and MMP9, and increased the cell cycle inhibitor CDKN1A (p21Cip1/Waf1). CTNNA3 is also frequently mutated in laryngeal carcinomas and low-expressed in urothelial carcinoma of the bladder.
Protein description
Other α-catenins, CTNNA1and CTNNA2 are also frequently mutated (loss of function) in various cancers
Protein description
CTNNA3 is inhibited by MIR425 (He et al., 2016; Stahn et al., 2016)..
Germinal mutations

Result of the Chromosomal Anomaly


t(10;10)(p12;q21) CTNNA3/ARHGAP21 but no fusion transcript was detectable.


Pubmed IDLast YearTitleAuthors
268825632016CTNNA3 is a tumor suppressor in hepatocellular carcinomas and is inhibited by miR-425.He B et al
277656352016Molecular Analysis of Hybrid Neurofibroma/Schwannoma Identifies Common Monosomy 22 and α-T-Catenin/CTNNA3 as a Novel Candidate Tumor Suppressor.Stahn V et al
222371062012The genetic basis of early T-cell precursor acute lymphoblastic leukaemia.Zhang J et al


Fusion gene



Jean-Loup Huret

t(10;10)(p12;q21) CTNNA3/ARHGAP21

Atlas Genet Cytogenet Oncol Haematol. 2018-08-01

Online version: http://atlasgeneticsoncology.org/haematological/1835/t(10;10)(p12;q21)