| Written | 2017-09 | Nathalie Nadal |
| 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. |
| Keywords | Chromosome 10; chromosome 14; NFKB2; IGH; Splenic marginal zone B-cell lymphoma; Multiple myeloma; Chronic lymphocytic leukemia |
| Identity |
| ICD-Topo | C420,C421,C424 |
| ICD-Morpho | 9732/3 Plasma cell myeloma / Multiple myeloma |
| ICD-Morpho | 9823/3 Chronic lymphocytic leukaemia /small lymphocytic lymphoma |
| ICD-Morpho | 9689/3 |
| ICD-Morpho | 9811/3 B lymphoblastic leukaemia/lymphoma, NOS |
| Atlas_Id | 2019 |
| 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). |
 | |
| 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 | |
| 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lymphomas, splenic marginal zone B-cell lymphomas in particular (Solé et al., 2001; Lefebvre et al., 2007, Nadal, unpublished observation) and also, but less frequently, in intermediate and high risk lymphomas (Neri et al., 1991).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 | NFKB2 |
| Location | 10q24.32 |
| Note | Alias: LYT-10, NF-kB2, p105, p49/p100, p52 |
| Dna / Rna | 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 | 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 |
| Heterogeneous chromosomal aberrations generate 3' truncations of the NFKB2/lyt-10 gene in lymphoid malignancies. |
| Migliazza A, Lombardi L, Rocchi M, Trecca D, Chang CC, Antonacci R, Fracchiolla NS, Ciana P, Maiolo AT, Neri A. |
| Blood. 1994 Dec 1;84(11):3850-60. |
| PMID 7949142 |
| B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-kappa B p50 |
| Neri A, Chang CC, Lombardi L, Salina M, Corradlni P, Maiolo AT, Chaganti RSK, Dalla-Favera R. |
| Cell. 1991 Dec 20;67(6):1075-87. |
| PMID 1760839 |
| Transcription factors of the alternative NF-?B pathway are required for germinal center B-cell development |
| De Silva NS, Anderson MM, Carettea A, Silvaa K, Heisea N, Bhagata G, Klein U. |
| PNAS | August 9, 2016 | vol. 113 | no. 32 | 9063-9068. |
| PMID 27457956 |
| Molecular impact of selective NFKB1 and NFKB2 signaling on DLBCL phenotype |
| Guo X, Koff JL, Moffitt AB, Cinar M, Ramachandiran S, Chen Z, Switchenko JM, Mosunjac M, Neill SG, Mann KP, Bagirov M, Du Y, Natkunam Y, Khoury HJ, Rossi MR, Harris W, Flowers CR, LossosI S, Boise LH, Dave SS, Kowalski J, Bernal-Mizrachi L. |
| Oncogene. 2017 Apr 3. doi: 10.1038/onc.2017.90. [Epub ahead of print] |
| PMID 28368397 |
| Composite splenic marginal zone lymphoma and mantle cell lymphoma arising from 2 independent B-cell clones |
| Lefebvre C, Fabre B, Vettier C, Rabin L, Florin A, Wang J, Gressin R, Jacob MC, Callanan M, Leroux D. |
| Human Pathology (2007) 38, 660- 667. |
| PMID 17134739 |
| Chromosome aberrations in a series of 120 multiple myeloma cases with abnormal karyotypes. |
| Mohamed AN, Bentley G, Bonnett ML, Zonder J, Al-Katib A. |
| Am J Hematol. 2007 Dec;82(12):1080-7. |
| PMID 17654686 |
| Pathogenesis of human B cell lymphomas. |
| Shaffer AL 3rd, Young RM, Staudt LM |
| Annu Rev Immunol. 2012;30:565-610. Review |
| PMID 22224767 |
| Splenic marginal zone B-cell lymphomas: two cytogenetic subtypes, one with gain of 3q and the other with loss of 7q |
| Solé F, Salido M, Espinet B, Garcia JL, Martinez Climent JA, Granada I, Hernández JM, Benet I, Piris MA, Mollejo M, Martinez P, Vallespè T, Domingo A, Serrano S, Woessner S, Florensa L. |
| Haematologica. 2001 Jan;86(1):71-7. |
| PMID 11146574 |
| Citation |
| This paper should be referenced as such : |
| Nathalie Nadal |
| t(10;14)(q24;q32) NFKB2/IGH |
| Atlas Genet Cytogenet Oncol Haematol. 2018;22(11):448-450. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Anomalies/t1014q24q32NFKB2IGHID2019.html |
| Translocations implicated (Data extracted from papers in the Atlas) |
| t(10;14)(q24;q32) NFKB2/IGH | |
| External links |
| 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 Jul 8 15:28:01 CEST 2019 |
For comments and suggestions or contributions, please contact us