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

2019-10-01   Jean Loup Huret 

1.jean-loup.huret@atlasgeneticsoncology.org

Abstract

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

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 description
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 description
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

Description

STRN3 exon 9 was fused to JAK2 exon 17.835 amino acids. The N-term striatin domain was fused to the pseudo kinase domain and C-term Tyr kinase domain). Sequence junction: .ARAEEV_LQER....

Bibliography

Pubmed IDLast YearTitleAuthors
28634811985Problem-oriented article summary.Berry EM et al
293794702017Mechanistic Insights into Regulation of JAK2 Tyrosine Kinase.Hubbard SR et al
287903872017GSK3β and ERK regulate the expression of 78 kDa SG2NA and ectopic modulation of its level affects phases of cell cycle.Pandey S et al
228978472012Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia.Roberts KG et al

Summary

Fusion gene

STRN3/JAK2

Citation

Jean Loup Huret

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

Atlas Genet Cytogenet Oncol Haematol. 2019-10-01

Online version: http://atlasgeneticsoncology.org/haematological/1683/t(9;14)(p24;q12)-strn3-jak2

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