To be noted, a missense mutation in DCLRE1C

ARHGAP21

10p12.1

The transcript has 26 exons.

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).

10q21.3

The transcript has 18 exons.

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.

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

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.

Other α-catenins, CTNNA1and CTNNA2 are also frequently mutated (loss of function) in various cancers

CTNNA3 is inhibited by MIR425 (He et al., 2016; Stahn et al., 2016)..