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t(5;12)(p13;p13) NIPBL/ETV6

Written2012-11Etienne De Braekeleer, Juan Ramón González García, Janet Margarita Soto Padilla, Carlos Cordova Fletes, Frédéric Morel, Nathalie Douet-Guilbert, Marc De Braekeleer
Cytogenetics Laboratory, Faculty of Medicine, University of Brest, France (EDB, FM, NDG, MDB); Division de Genetica. Centro de Investigacion Biomedica de Occidente. IMSS. Guadalajara, Jalisco, Mexico (JRGG); Departamento de Hematologia. HUMAE-H. Pediatria. Centro Medico Nacional de Occidente. IMSS. Guadalajara, Jalisco, Mexico (JMSP); Unidad de Biologia Molecular, Genomica y Secuenciacion, Centro de Investigacion y Desarrollo en Ciencias de la Salud, Universidad Autonoma de Nuevo Leon, Monterrey, Nuevo Leon, Mexico (CCF)

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ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
Atlas_Id 1616

Clinics and Pathology

Disease Acute myeloid leukemia (AML-M7)
Epidemiology This is a rare chromosomal rearrangement, only reported twice, without molecular characterization (Sessarego et al., 1989; Shimizu et al., 1991).
Clinics A 5-year old girl seen for paleness, hypertrophic amygdala, bilateral cervical adenopathies, splenomegaly, and anemia.
Cytology Blast morphology was indicative of acute megakaryoblastic leukemia; immunophenotype: CD7+, CD33+, CD34+.
Pathology Bone marrow was hypercellular, with 100% blasts.
Treatment The patient received standard induction chemotherapy leading to complete remission followed by consolidation, then maintenance therapy.
Evolution The patient relapsed 24 months later, alive 32 months following diagnosis.


The t(5;12)(p13;p13) involves the ETV6 gene (12p13), a transcription factor frequently rearranged in myeloid and lymphoid leukemias. More than 30 ETV6 fusion gene partners have been described. Most translocations involving ETV6 generate fusion genes that lead to the activation of transcription factors or kinases but other mechanisms are also known (loss of function of the fusion gene, affecting ETV6 and the partner gene, activation of a proto-oncogene in the vicinity of a chromosomal translocation and dominant negative effect of the fusion protein over transcriptional repression mediated by wild-type ETV6) (De Braekeleer et al., 2012).


Cytogenetics Morphological t(5;12)(p13;p13) as the sole abnormality at diagnosis and relapse.
  GTG banding showing chromosomes 5 and 12 and the derivatives der(5) and der(12).
Cytogenetics Molecular FISH showed that the breakpoint on 12p13 was located in ETV6. To confirm the position of the breakpoint on chromosome 5, BACs located at 5p13 were used as probes in FISH experiments. Analysis on BM cells of the patient with RP11-140A7 showed that one signal hybridized to the normal chromosome 5, and the other split and hybridized to both der(5) and der(12). Co-hybridization with the RP11-140A7 clone and an ETV6 probe showed two yellow fusion signals. RP11-140A7 contains the NIPBL gene.

Genes involved and Proteins

Gene NameETV6 (ets variant 6)
Location 12p13.2
Protein The ETV6 gene encodes a transcription factor frequently rearranged in myeloid and lymphoid leukemias (De Braekeleer et al., 2012).
Gene NameNIPBL (NIPBL, cohesin loading factor)
Location 5p13.2
Note Mutations in NIPBL (Nipped-B homolog (Drosophila), alias Scc2 "sister chromatid cohesion 2 homolog (yeast)") result in Cornelia de Lange syndrome, a disorder characterized by dysmorphic facial features, growth delay, limb reduction defects, and mental retardation (Krantz et al., 2004; Tonkin et al., 2004).
Dna / Rna The NIPBL gene contains 47 exons spanning 188 kb, with the coding sequence starting in exon 2. Two different isoforms are generated by two transcript variants. A first transcript, starting in exon 2, continues to exon 47 and the second transcript continues to an expanded variant of exon 46.
Protein The first transcript leads to a 2804 amino acids isoform and the second transcript to a 2697 amino acids isoform. Both isoforms are identical from amino acid 1 to 2683 while the C-terminal ends are unrelated. The NIPBL protein is a complex molecule containing, among others, a nuclear localization signal, a nuclear export signal, 5 HEAT repeats and a DNA-binding domain. The NIPBL protein is a subunit of the cohesin loading complex that mediates cohesion of sister chromatids (Ciosk et al., 2000). NIPBL also represses promoter activity via the recruitment of histone deacetylases (Jahnke et al., 2008).

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.


Cohesin's binding to chromosomes depends on a separate complex consisting of Scc2 and Scc4 proteins.
Ciosk R, Shirayama M, Shevchenko A, Tanaka T, Toth A, Shevchenko A, Nasmyth K.
Mol Cell. 2000 Feb;5(2):243-54.
PMID 10882066
ETV6 fusion genes in hematological malignancies: a review.
De Braekeleer E, Douet-Guilbert N, Morel F, Le Bris MJ, Basinko A, De Braekeleer M.
Leuk Res. 2012 Aug;36(8):945-61. doi: 10.1016/j.leukres.2012.04.010. Epub 2012 May 12. (REVIEW)
PMID 22578774
The Cohesin loading factor NIPBL recruits histone deacetylases to mediate local chromatin modifications.
Jahnke P, Xu W, Wulling M, Albrecht M, Gabriel H, Gillessen-Kaesbach G, Kaiser FJ.
Nucleic Acids Res. 2008 Nov;36(20):6450-8. doi: 10.1093/nar/gkn688. Epub 2008 Oct 14.
PMID 18854353
Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B.
Krantz ID, McCallum J, DeScipio C, Kaur M, Gillis LA, Yaeger D, Jukofsky L, Wasserman N, Bottani A, Morris CA, Nowaczyk MJ, Toriello H, Bamshad MJ, Carey JC, Rappaport E, Kawauchi S, Lander AD, Calof AL, Li HH, Devoto M, Jackson LG.
Nat Genet. 2004 Jun;36(6):631-5. Epub 2004 May 16.
PMID 15146186
Cytogenetic follow-up after bone marrow transplantation for Philadelphia-positive chronic myeloid leukemia.
Sessarego M, Frassoni F, Defferrari R, Bacigalupo A, Miceli S, Mareni C, Ajmar F.
Cancer Genet Cytogenet. 1989 Oct 15;42(2):253-61.
PMID 2790760
A case of mixed lineage acute non-lymphocytic leukemia with t(5;12)(p13;p13).
Shimizu S, Tsunematsu Y, Fujimoto J, Mizutani S, Kaneko Y.
Jpn J Clin Oncol. 1991 Aug;21(4):314-7.
PMID 1942561
NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.
Tonkin ET, Wang TJ, Lisgo S, Bamshad MJ, Strachan T.
Nat Genet. 2004 Jun;36(6):636-41. Epub 2004 May 16.
PMID 15146185
Identification of NIPBL, a new ETV6 partner gene in t(5;12) (p13;p13)-associated acute megakaryoblastic leukemia.
de Braekeleer E, Auffret R, Garcia JR, Padilla JM, Fletes CC, Morel F, Douet-Guilbert N, de Braekeleer M.
Leuk Lymphoma. 2013 Feb;54(2):423-4. doi: 10.3109/10428194.2012.706288. Epub 2012 Jul 18.
PMID 22734863


This paper should be referenced as such :
De, Braekeleer E ; Gonzalez, Garcia JR ; Soto, Padilla JM ; Cordova, Fletes C ; Morel, F ; Douet-Guilbert, N ; De, Braekeleer M
t(5;12)(p13;p13) NIPBL/ETV6
Atlas Genet Cytogenet Oncol Haematol. 2013;17(3):206-208.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]

Genes ETV6

Translocations implicated (Data extracted from papers in the Atlas)

 t(5;12)(p13;p13) NIPBL/ETV6

External links

Mitelman databaset(5;12)(p13;p13)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9861/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

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