t(6;10)(q22;q24) NFKB2/ROS1

2019-09-01   Tatiana Gindina 

1.R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation at Pavlov First Saint-Petersburg State Medical University, Saint-Petersburg, Russian Federation / e-mail: tatgindina@gmail.com

Abstract

Review on t(6;10)(q22;q24), with data on the genes involved.

Clinics and Pathology

Disease

Anaplastic large cell lymphoma, ALK negative

Note

Only one case to date (Crescenzo et al., 2015). No individual data, no clinical data.

Prognosis

No data

Genes Involved and Proteins

Gene name
NFKB2
Location
10q24.32
Protein description
The gene encodes a subunit of the transcription factor complex nuclear factor-kappa-B. NFKB2 is a rapidly acting primary transcription factor found in all cell types. It is involved in the cellular responses to stimuli such as cytokines and stress and plays a key role in regulating the immunological response to infections.
Gene name
ROS1
Location
6q22.1
Protein description
This proto-oncogene belongs to the subfamily of tyrosine kinase insulin receptor genes and expresses in a variety of tumor cell lines. ROS1 is an integral membrane protein with tyrosine kinase activity, that may function as a growth or differentiation factor receptor.

Result of the Chromosomal Anomaly

Note

5 NFKB2 - 3 ROS1

Description

Nucleotide sequence analyses revealed that NFKB2 (exon 1-13) is fused to the intracytoplasmic domain of ROS1 accompanied by loss of the NFKB2 ankyrin region, that is necessary for the translation of constitutively active NFKB-fusion proteins and its oncogenic role [Crescenzo et al., 2015].
Atlas Image

Oncogenesis

NFKB2/ROS1 is a chimeric transcription factor with oncogenic potential that leads to the constitutive activation of STAT3 in the absence of either JAK-STAT3 mutations. The ectopic expression of NFKB2/ROS1 is associated with the phosphorylation of JAK (JAK2 - JAK3) and STAT3. NFKB2/ROS1 fusion induces the expression of genes involved in membrane trafficking, replication, protein export, TNF signaling, T cell activation. This, in turn, may lead to a widespread derangement of several metabolic and signaling pathways, which ultimately concur to neoplastic transformation [Crescenzo et al., 2015, Tabbo et al, 2016].

Bibliography

Pubmed IDLast YearTitleAuthors
258731742015Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma.Crescenzo R et al
269437762016Oncogenic kinase fusions: an evolving arena with innovative clinical opportunities.Tabbò F et al

Summary

Fusion gene

NFKB2/ROS1

Citation

Tatiana Gindina

t(6;10)(q22;q24) NFKB2/ROS1

Atlas Genet Cytogenet Oncol Haematol. 2019-09-01

Online version: http://atlasgeneticsoncology.org/haematological/1720/t(6;10)(q22;q24)-nfkb2-ros1