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

Written2018-08Jean-Loup Huret
jean-loup.huret@atlasgeneticsoncology.org

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

Keywords Chromosome 10; CTNNA3; ARHGAP21; Early T-cell precursor acute lymphoblastic leukaemia

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424
ICD-Morpho 9837/3 T lymphoblastic leukaemia/lymphoma
Atlas_Id 1835

Clinics and Pathology

Disease Early T-cell precursor acute lymphoblastic leukaemia
Epidemiology Only one case to date, a 7-year old boy (Zhang et al. 2012).
Evolution Outcome: relapse with lineage switch at 13 months after diagnosis; the patient died at 25 months post diagnosis.

Cytogenetics

Cytogenetics Morphological The karyotype was complex, with a constitutional inv(2)(p11.2q13), a del(1p), and other abnormalities.

Genes involved and Proteins

Note To be noted, a missense mutation in DCLRE1C
Gene NameARHGAP21
Location 10p12.1
Dna / Rna The transcript has 26 exons.
Protein 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 NameCTNNA3
Location 10q21.3
Dna / Rna The transcript has 18 exons.
Protein 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)..
Germinal mutations

Result of the chromosomal anomaly

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

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.

Bibliography

ARHGAP21 (Rho GTPase activating protein 21);
Ferreira Pissarra M, Olalla Saad ST, Lazarini M
Atlas Genet Cytogenet Oncol Haematol. in press On line version : http://AtlasGeneticsOncology.org/Genes/ARHGAP21ID43137ch10p12.html
 
CTNNA3 is a tumor suppressor in hepatocellular carcinomas and is inhibited by miR-425.
He B, Li T, Guan L, Liu FE, Chen XM, Zhao J, Lin S, Liu ZZ, Zhang HQ.
Oncotarget. 2016 Feb 16;7(7):8078-89. doi: 10.18632/oncotarget.6978.
PMID 26882563
 
Molecular Analysis of Hybrid Neurofibroma/Schwannoma Identifies Common Monosomy 22 and ?-T-Catenin/CTNNA3 as a Novel Candidate Tumor Suppressor.
Stahn V, Nagel I, Fischer-Huchzermeyer S, Oyen F, Schneppenheim R, Gesk S, Bohring A, Chikobava L, Young P, Gess B, Werner M, Senner V, Harder A.
Am J Pathol. 2016 Dec;186(12):3285-3296. doi: 10.1016/j.ajpath.2016.08.019. Epub 2016 Oct 17.
PMID 27765635
 
The genetic basis of early T-cell precursor acute lymphoblastic leukaemia.
Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, Easton J, Chen X, Wang J, Rusch M, Lu C, Chen SC, Wei L, Collins-Underwood JR, Ma J, Roberts KG, Pounds SB, Ulyanov A, Becksfort J, Gupta P, Huether R, Kriwacki RW, Parker M, McGoldrick DJ, Zhao D, Alford D, Espy S, Bobba KC, Song G, Pei D, Cheng C, Roberts S, Barbato MI, Campana D, Coustan-Smith E, Shurtleff SA, Raimondi SC, Kleppe M, Cools J, Shimano KA, Hermiston ML, Doulatov S, Eppert K, Laurenti E, Notta F, Dick JE, Basso G, Hunger SP, Loh ML, Devidas M, Wood B, Winter S, Dunsmore KP, Fulton RS, Fulton LL, Hong X, Harris CC, Dooling DJ, Ochoa K, Johnson KJ, Obenauer JC, Evans WE, Pui CH, Naeve CW, Ley TJ, Mardis ER, Wilson RK, Downing JR, Mullighan CG.
Nature. 2012 Jan 11;481(7380):157-63. doi: 10.1038/nature10725.
PMID 22237106
 

Citation

This paper should be referenced as such :
Huret JL
t(10;10)(p12;q21) CTNNA3/ARHGAP21;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Anomalies/t1010p12q21ID1835.html


Translocations implicated (Data extracted from papers in the Atlas)

 t(10;10)(p12;q21) CTNNA3/ARHGAP21

External links

Mitelman databaset(10;10)(p12;q21) [Case List]    t(10;10)(p12;q21) [Transloc-MCList] CTNNA3/ARHGAP21 [Fusion-MCList]
arrayMap (UZH-SIB Zurich)Morph ( 9837/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
 
 
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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