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Leukaemia Section Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Leukaemia Section Short Communication t(4;9)(q21.22;p24) SEC31A/JAK2 Julie Sanford Biggerstaff Idaho Cytogenetics Diagnostic Laboratory, Boise, ID 83706, USA; [email protected] Published in Atlas Database: April 2017 Online updated version : http://AtlasGeneticsOncology.org/Anomalies/t0409q21p24ID1682.html Printable original version : http://documents.irevues.inist.fr/bitstream/handle/2042/68905/04-2017-t0409q21p24ID1682.pdf DOI: 10.4267/2042/68905 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2018 Atlas of Genetics and Cytogenetics in Oncology and Haematology Abstract Cytogenetics Review on t(4;9)(q21.22;p24) SEC31A/JAK2, with data on clinics, and the genes involved. Cytogenetics morphological KEYWORDS JAK2 breakapart (commonly available). Chromosome 4; chromosome 9; translocation; SEC31A; JAK2; Hodgkin Lymphoma Genes involved and Clinics and pathology proteins SEC31A (SEC31 homolog A, COPII Disease coat complex component) Hodgkin Lymphoma Location Phenotype/cell stem origin 4q21.22 Hodgkin and Reed-Sternberg cells, which derive DNA/RNA from pre-apoptotic crippled germinal center (GC) B- gene is 72,606 bp with 25 exons; transcribed from cells, are positive for CD30, CD15, CD40 and the - strand; coding region is 62,863 bp with 24 IRF4/MUM1 exons Epidemiology Protein Hodgkin lymphoma itself is common, but this 1166 amnio acids. Protein transport protein SEC31A particular translocation may be rare within the is ubiquitously expressed and forms part of the coat disorder. However, it is not often assayed for; found protein complex II (COPII) which is comprised of at in 2/131 cHL cases examined: a M/31 with nodular least four other proteins in addition to SEC31A this sclerosis cHL, alive 60 mths after diagnosis; and a complex is involved in formation of transport M/83 with lymphocyte-depleted cHL who died at vesicles from the ER to Golgi. Protein localized to day 14 (Van Roosbroeck et al, 2011). the cytoplasmic side of the cell membrane and is GTP-dependent. Treatment JAK2 (janus kinase 2) SEC31A/JAK2 acts as a constitutively activated Location tyrosine kinase and is sensitive to JAK2 inhibition 9p24.1 Prognosis DNA/RNA Yet unknown. Atlas Genet Cytogenet Oncol Haematol. 2018; 22(5) 216 t0409q21p24ID1682 143,098 bp with 24 exons; transcribed from the + strand; coding region is 104,804 bp with 23 exons. FISH using JAK2 and SEC31A breakapart probes, Protein rtPCR or RNAseq. Protein is 1132 amino acids with multiple functional Fusion protein domains; regulated by auto-phosphorylation. Non- receptor protein tyrosine kinase, ubiquitously Oncogenesis expressed. The fusion protein is a constitutively activated tyrosine kinase: JAK2 activation is mediated by a Germinal mutations domain region of SEC31A that lies between the WD- Germline mutations associated with autosomal 40-like and proline-rich domains of the protein (Van dominant Familial Thrombocythemia Roosbroeck et al, 2011). Somatic mutations 'Gain of Function' V617F mutation and mutations in References exon 12 of the gene common in patients with Polycythemia Vera, Myelofibrosis with Myeloid Tang BL, Zhang T, Low DY, Wong ET, Horstmann H, Hong W. Mammalian homologues of yeast sec31p. An Metaplasia or idiopathic erythrocytosis. ubiquitously expressed form is localized to endoplasmic reticulum (ER) exit sites and is essential for ER-Golgi Result of the chromosomal transport. J Biol Chem. 2000 May 5;275(18):13597-604 Van Roosbroeck K, Cox L, Tousseyn T, Lahortiga I, Gielen anomaly O, Cauwelier B, De Paepe P, Verhoef G, Marynen P, Vandenberghe P, De Wolf-Peeters C, Cools J, Wlodarska I. Hybrid gene JAK2 rearrangements, including the novel SEC31A-JAK2 Note fusion, are recurrent in classical Hodgkin lymphoma. Blood. Fusion results in 5' SEC31A fused to 3' partner gene 2011 Apr 14;117(15):4056-64 JAK2 This article should be referenced as such: Description Sanford Biggerstaff JA. t(4;9)(q21.22;p24) Exon 22 SEC31A is fused with exon 17 of JAK2 in SEC31A/JAK2. Atlas Genet Cytogenet Oncol the two reported cases (Van Roosbroeck et al, 2011) Haematol. 2018; 22(5):216-217. Detection Atlas Genet Cytogenet Oncol Haematol. 2018; 22(5) 217 .
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