t(10;14)(q24;q32) NFKB2/IGH

2017-09-01   Nathalie Nadal 

1.Service de génétique chromosomique et moléculaire, CHU de Dijon, France; nathalie.nadal@chu-dijon.fr

Abstract

Review on t(10;14)(q24;q32) NFKB2/IGH, with data on clinics, and the genes involved.

Clinics and Pathology

Disease

B-cell lymphomas: The band 10q24 is involved in 7% of low-grade B-cell lymphomas, splenic marginal zone B-cell lymphomas in particular (Solé et al., 2001; Lefebvre et al., 2007, Nadal, unpublished observation) and also, but less frequently, in intermediate and high risk lymphomas (Neri et al., 1991).
Other chronic lympho proliferative diseases: Multiple myeloma (Migliazza et al., 1994; Mohamed et al.), chronic lymphocytic leukemia (CLL) (Migliazza, 1994)

Prognosis

Unknown.

Cytogenetics

Cytogenetics morphological

The t(10;14)(q24;q32) is a rare but recurrent abnormality in lymphoid malignancies.

Additional anomalies

The following known recurrent abnormalities were found in one case each: +3, +7, and +12.

Genes Involved and Proteins

Gene name
Location
10q24.32
Note
Alias: LYT-10, NF-kB2, p105, p49/p100, p52
Dna rna description
NFKB2 gene is a member of NFKB gene family. NFKB2 gene encodes for the precursor p100/p52 from which the active p52 subunit is formed.
Protein description
P52 is a member of the NFKB family transcription factors that are formed by the homo/dimerization of the subunits of the NFKB family. After dimerization with the subunit RELB, P52 migrates to the nucleus where they activate the transcription of target genes.
Localization: cytosol for p100 product and nucleus for the final product p52 after activation
P52 is a component of the non-canonical NF-KB pathway which plays a role in the control of the last stages of B-Cells development (maintenance of the Germinal Center (GC) reaction and Plasma cell development) (Shaffer et al., 2012; De Silva et al., 2017).
Gene name
IGH (Immunoglobulin Heavy chain)
Location
14q32

Result of the Chromosomal Anomaly

Description

t(10;14)(q24;q32) translocation juxtaposes IGH constant region gene with NFKB2 gene (Neri et al., 1991). The fusion gene NFKB2/IGH results in the constitutional activation of the non-canonical NFKB pathway. The reciprocal fusion gene IGH/NFKB2 is not transcribed.

Note

NFKB2 gene encodes for the protein P52 which contains a DNA binding domain and an Ankyrin domain. The Ankyrin domain is thought to retain p100/P52 in the cytoplasm and thus prevent the DNA binding.
The band in 10q24 can be involved in different types of rearrangement such as cryptic deletion or translocation t(10;14). The common consequence is a truncated protein which retains the DNA binding domain but lack the Ankyrin domain (Migliazza et al., 1994). These rearrangements result in a constitutive activation of P52 which lead to the activation of the non-canonical NFKB pathway and thus promote B-cell malignancies (de silva, 2017; Guo, 2017).

Expression localisation

Nucleus.

Bibliography

Pubmed IDLast YearTitleAuthors
79491421994Heterogeneous chromosomal aberrations generate 3' truncations of the NFKB2/lyt-10 gene in lymphoid malignancies.Migliazza A et al
17608391991B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-kappa B p50.Neri A et al
274579562016Transcription factors of the alternative NF-κB pathway are required for germinal center B-cell development.De Silva NS et al
283683972017Molecular impact of selective NFKB1 and NFKB2 signaling on DLBCL phenotype.Guo X et al
171347392007Composite splenic marginal zone lymphoma and mantle cell lymphoma arising from 2 independent B-cell clones.Lefebvre C et al
176546862007Chromosome aberrations in a series of 120 multiple myeloma cases with abnormal karyotypes.Mohamed AN et al
222247672012Pathogenesis of human B cell lymphomas.Shaffer AL 3rd et al
111465742001Splenic marginal zone B-cell lymphomas: two cytogenetic subtypes, one with gain of 3q and the other with loss of 7q.Solé F et al

Summary

Fusion gene

NFKB2/IGH

Note

The t(10;14)(q24.31;q11) in T-ALL involves the gene TLX1 at the band 10q24.31 and not NFKB2 at band 10q24.32 (Neri et al., 1991).
Atlas Image
Conventional karyotype: Partial G and R banded karyotype. The derivative chromosomes are denoted with arrows. G-Banding, Courtesy Nathalie Nadal. R-banding, Courtesy Christine Lefebvre (upper row), N Nadal (lower row); FISH: top: WCP7R/WCP10G (aquarius); XL t(11;14)(IGH/CCND1) (metasystems) 11q13R/14q32G - Courtesy Christine Lefebvre

Citation

Nathalie Nadal

t(10;14)(q24;q32) NFKB2/IGH

Atlas Genet Cytogenet Oncol Haematol. 2017-09-01

Online version: http://atlasgeneticsoncology.org/haematological/2019/t(10;14)(q24;q32)

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