t(9;14)(p24;q12) STRN3/JAK2

Abstract

Review on t(9;14)(p24;q12), with data on clinics, and the genes involved.

Keywords

Chromosome 9; Chromosome 14; STRN3; JAK2

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo	C420,C421,C424
ICD-Morpho	9811/3 B lymphoblastic leukaemia/lymphoma, NOS
Atlas_Id	1683

Clinics and Pathology

Disease	Acute lymphoblastic leukemia (ALL).
Epidemiology	Only 1 case to date, a 12 year-old female patient with high-risk B-lineage ALL (Roberts et al., 2012).

Genes involved and Proteins

Note	There was a IKZF1 deletion and p.Leu117fs (Frame shift) mutation.

Gene Name	JAK2 (janus kinase 2)
Location	9p24.1
Protein	1132 amino acids (aa); 130,7 kDa; JAK2 contains an Interaction with cytokine/interferon/growth hormone receptors region (aa 1-239), a FERM domain: (aa 37-380), a central Src homology 2 (SH2) domain (aa 401-482), and two C-terminal domains: a tyrosine kinase domain JH1 (also termed PTK or TyrKc domain (aa 545-809)), and a tyrosine kinase-like domain JH2 (also termed STYKc (aa 849-1124)). JAK Homology domains are the following: JH7 aa 25-137; JH6: aa 144-284; JH5: aa 288-309; JH4: aa 322-440; JH3: aa 451-538; JH2: aa 543-824; JH1: aa 836-1123. JAK2 is a member of the Janus kinase (JAKs) family of non-receptor protein tyrosine kinases ( JAK1, JAK2, JAK3, TYK2) .Janus kinases are protein tyrosine kinases of the non-receptor type that associates with the intracellular domains of cytokine receptors including the receptors for interleukins, interferons, growth hormone, erythropoietin, and leptin. Mediates signaling transduction. Janus kinases are constitutively bound to the cytoplasmic region of cytokine receptors. Binding of cytokines induces cytokine receptor dimerization, facilitating trans-phosphorylation of the associated JAKs and JAK/STAT signaling. Erythropoietin receptor (EPOR) and growth hormone receptor (GHR) bind JAK2 exclusively. JAK2 is frequently mutated in myeloproliferative disorders. JAK2-V617F mutation occurs at the stem cell level and is present in hematopoietic stem cell progenitors (Strehl et al., 2006; Gangat and Tefferi, 2008; Hubbard, 2017).

Gene Name	STRN3 (striatin 3)
Location	14q12
Protein	797 amino acids (aa), contains caveolin-binding and calmodulin-binding regions in the N-term (aa 71-79 and 166-183 respectively), a coiled-coil domain (aa 77-136, which allow homo- and hetero-oligomerization), and 6 WD repeats (from aa 478 to aa 796; WD-repeat domain enables proteins to establish multiple protein-protein interactions). STRN3 is a member of striatin family ( STRN, STRN3, STRN4) which function as scaffold in different signal transduction pathways STRN and STRN3 are the constituents of a multiprotein assembly called striatin-interacting phosphatase and kinase (STRIPAK). STRIPAK are regulators of cell cycle, differentiation, metabolism, immune regulation, Golgi assembly, cell polarity, cell migration, etc. STRN3 protects cells from oxidative stress. SG2NA is involved in maintaining ER homeostasis. Downregulation of SG2NA reduces the level of CCND1 (cyclin D1) and retains a population of cells in the G1 phase, and its overexpression extends G2 (Jain et al., 2017; Pandey et al., 2018).

Result of the chromosomal anomaly

Hybrid gene

Description	STRN3 exon 9 was fused to JAK2 exon 17.

Fusion Protein

Description	835 amino acids. The N-term striatin domain was fused to the pseudo kinase domain and C-term Tyr kinase domain). Sequence junction: .ARAEEV_LQER....

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

Problem-oriented article summary

Berry EM

Lancet 1985 Aug 24;2(8452):452

PMID 2863481

Mechanistic Insights into Regulation of JAK2 Tyrosine Kinase

Hubbard SR

Front Endocrinol (Lausanne) 2018 Jan 5;8:361

PMID 29379470

Mechanistic Insights into Regulation of JAK2 Tyrosine Kinase.

Hubbard SR.

Front Endocrinol (Lausanne). 2018 Jan 5;8:361. doi: 10.3389/fendo.2017.00361. eCollection 2017. Review.

PMID 29379470

Strehl, S

JAK2 (janus kinase 2)

Atlas Genet Cytogenet Oncol Haematol. 2006;10(1):3-6.

Gangat N, Tefferi A

JAK2 mutations in myeloproliferative neoplasms

Atlas Genet Cytogenet Oncol Haematol. 2009;13(8):612-617.

GSK3beta and ERK regulate the expression of 78kDa SG2NA and ectopic modulation of its level affects phases of cell cycle

Pandey S, Talukdar I, Jain BP, Tanti GK, Goswami SK

Sci Rep 2017 Aug 8;7(1):7555

PMID 28790387

Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia

Roberts KG, Morin RD, Zhang J, Hirst M, Zhao Y, Su X, Chen SC, Payne-Turner D, Churchman ML, Harvey RC, Chen X, Kasap C, Yan C, Becksfort J, Finney RP, Teachey DT, Maude SL, Tse K, Moore R, Jones S, Mungall K, Birol I, Edmonson MN, Hu Y, Buetow KE, Chen IM, Carroll WL, Wei L, Ma J, Kleppe M, Levine RL, Garcia-Manero G, Larsen E, Shah NP, Devidas M, Reaman G, Smith M, Paugh SW, Evans WE, Grupp SA, Jeha S, Pui CH, Gerhard DS, Downing JR, Willman CL, Loh M, Hunger SP, Marra MA, Mullighan CG

Cancer Cell 2012 Aug 14;22(2):153-66

PMID 22897847

Citation

This paper should be referenced as such :

Jean Loup Huret

t(9;14)(p24;q12) STRN3/JAK2

Atlas Genet Cytogenet Oncol Haematol. 2020;24(8):320-321.

Free journal version : [ pdf ]   [ DOI ]

On line version : http://AtlasGeneticsOncology.org/Anomalies/t0914p24q12STRN3-JAK2ID1683.html

Translocations implicated (Data extracted from papers in the Atlas)

	t(9;14)(p24;q12) STRN3/JAK2

External links

Mitelman database	t(9;14)(p24;q12)
arrayMap (UZH-SIB Zurich)	Morph ( 9811/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]

REVIEW articles	automatic search in PubMed
Last year articles	automatic search in PubMed
All articles	automatic search in PubMed

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Sep 7 15:07:57 CEST 2020

For comments and suggestions or contributions, please contact us