| Written | 2017-04 | Tatiana Gindina |
| Gorbacheva Memorial Institute of 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;11)(q24.1;p15.5), with data on the genes involved |
| Keywords | Chromosome 6; chromosome 11; Acute megakaryoblastic leukemia; T lymphoblastic leukaemia/lymphoma |
| Identity |
| ICD-Topo | C420,C421,C424 |
| ICD-Morpho | 9910/3 Acute megakaryoblastic leukaemia |
| ICD-Morpho | 9837/3 T lymphoblastic leukaemia/lymphoma |
| Atlas_Id | 1395 |
| Clinics and Pathology |
| Disease | Acute megakaryoblastic leukemia (M7 AML) and T lymphoblastic leukemia |
| Epidemiology | Only two cases to date: a 5-year-old female patient (Tosi et al, 2005) and a 26-year-old male patient (Romana et al, 2006). |
| Cytogenetics |
| Cytogenetics Molecular | FISH technique with the NUP98 probe and BAC RP11-900M13 probe has been used to confirm the translocation in the reported case (Romana et al, 2006). |
| Additional anomalies | The T-ALL adult patient showed an additional abnormality of 12p13 (Romana et al, 2006). |
| Genes involved and Proteins |
| Gene Name | CCDC28A (coiled-coil domain containing 28A) |
| Location | 6q24.1 |
| Protein | CCDC28A encodes a coiled-coil domain containing protein. The native CCDC28A protein has no recognizable similarity to other proteins or functional domains, and no function has so far been assigned to the coiled-coil domain, leaving the biological function of CCDC28A undetermined. |
| Gene Name | NUP98 (nucleoporin 98 kDa) |
| Location | 11p15.4 |
| Note | also known as C6orf80 and MGC131913 |
| Protein | NUP98 belongs to the nucleoporin gene family and encodes a 186 kDa precursor protein that undergoes autoproteolytic cleavage to produce a 98 kDa nucleoporin and 96 kDa nucleoporin. The 98 kDa nucleoporin contains a Gly-Leu-Phe-Gly repeat domain and participates in many cellular processes including nuclear import/export, mitotic progression, and regulation of gene expression. The 96 kDa nucleoporin is a component of the nuclear pore complex. |
| Result of the chromosomal anomaly |
| Note | NUP98/CCDC28A |
| Description | Nucleotide sequence analyses revealed an in-frame fusion between the 13th exon of NUP98 and the second exon of CCDC28A. A reciprocal CCDC28A/NUP98 fusion transcript was detected but is likely devoid of biological activity due to the lack of a predicted fusion protein (Petit et al, 2012). |
| Note | NUP98/CCDC28A |
 | |
| Schematic representation of the wild-type NUP98 and CCDC28 products and of the chimeric fusion protein NUP98-CCDC28. | |
| Oncogenesis | In mouse models it has been demonstrated that the enforced NUP98/CCDC28A expression promoted the proliferative and self-renewal capacities of hematopoietic progenitors and rapidly caused fatal myeloproliferative neoplasms and defects in the differentiaton of the erythro-megakaryocytic lineage. Although the leukemogenic mechanism remains unknown, NUP98/CCDC28A retains the NUP98 GLFG-repeats able to associate with core binding protein and/or EP300 and has a nuclear localization suggesting possible transactivation activity. The transformation mediated by NUP98/CCDC28A was not associated with deregulation of the HOXA-Meis1 pathway, a feature shared by a diverse set of NUP98 fusions. Additional investigation will be needed to elucidate the role of NUP98/CCDC28A in lymphoid transformation (Petit et al, 2012). |
| To be noted |
| Additional cases are needed to delineate the epidemiology of this rare entity: you are welcome to submit a paper to our new Case Report section. |
| Bibliography |
| Functional analysis of the NUP98-CCDC28A protein. |
| Petit A, Ragu C, Soler G, et al. |
| Haematologica. 2012; 97(3):379-387 |
| PMID 22058212 |
| NUP98 rearrangements in hematopoietic malignancies: a study of the Groupe Francophone de Cytogenetique Hematologique. |
| Romana SP, Radford-Weiss I, Abdelali RB, et al. |
| Leukemia. 2006; 20(4):696-706 |
| PMID 16467868 |
| Characterization of 6q abnormalities in childhood acute myeloid leukemia and identification of a novel t(6;11)(q24.1;p15.5) resulting in a NUP98-C6orf80 fusion in a case of acute megakaryoblastic leukemia. |
| Tosi S, Ballabio E, Teigler-Schlegel A, et al. |
| Genes, Chromosomes & Cancer. 2005; 44(3):225-232 |
| PMID 16028218 |
| Citation |
| This paper should be referenced as such : |
| Gindina T |
| t(6;11)(q24.1;p15.5) NUP98/CCDC28A; |
| Atlas Genet Cytogenet Oncol Haematol. in press |
| On line version : http://AtlasGeneticsOncology.org/Anomalies/t0611q24p15ID1395.html |
| Translocations implicated (Data extracted from papers in the Atlas) |
| t(6;11)(q24;p15) NUP98/CCDC28A | |
| 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 Sep 18 17:19:40 CEST 2017 |
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