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

2012-11-01   Juan Ramón González García , Janet Margarita Soto Padilla , Carlos Cordova Fletes , Frédéric Morel , Nathalie Douet-Guilbert , Marc De Braekeleer , Etienne De Braekeleer 

1.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)

Clinics and Pathology


This is a rare chromosomal rearrangement, only reported twice, without molecular characterization (Sessarego et al., 1989; Shimizu et al., 1991).


A 5-year old girl seen for paleness, hypertrophic amygdala, bilateral cervical adenopathies, splenomegaly, and anemia.


Blast morphology was indicative of acute megakaryoblastic leukemia; immunophenotype: CD7+, CD33+, CD34+.


Bone marrow was hypercellular, with 100% blasts.


The patient received standard induction chemotherapy leading to complete remission followed by consolidation, then maintenance therapy.


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).


Atlas Image
GTG banding showing chromosomes 5 and 12 and the derivatives der(5) and der(12).

Cytogenetics morphological

t(5;12)(p13;p13) as the sole abnormality at diagnosis and relapse.

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 name
ETV6 (ets variant 6)
Protein description
The ETV6 gene encodes a transcription factor frequently rearranged in myeloid and lymphoid leukemias (De Braekeleer et al., 2012).
Gene name
NIPBL (NIPBL, cohesin loading factor)
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 description
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 description
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).


Pubmed IDLast YearTitleAuthors
108820662000Cohesin's binding to chromosomes depends on a separate complex consisting of Scc2 and Scc4 proteins.Ciosk R et al
225787742012ETV6 fusion genes in hematological malignancies: a review.De Braekeleer E et al
188543532008The Cohesin loading factor NIPBL recruits histone deacetylases to mediate local chromatin modifications.Jahnke P et al
151461862004Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B.Krantz ID et al
27907601989Cytogenetic follow-up after bone marrow transplantation for Philadelphia-positive chronic myeloid leukemia.Sessarego M et al
19425611991A case of mixed lineage acute non-lymphocytic leukemia with t(5;12)(p13;p13).Shimizu S et al
151461852004NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.Tonkin ET et al
227348632013Identification of NIPBL, a new ETV6 partner gene in t(5;12) (p13;p13)-associated acute megakaryoblastic leukemia.de Braekeleer E et al


Juan Ramón González García ; Janet Margarita Soto Padilla ; Carlos Cordova Fletes ; Frédéric Morel ; Nathalie Douet-Guilbert ; Marc De Braekeleer ; Etienne De Braekeleer

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

Atlas Genet Cytogenet Oncol Haematol. 2012-11-01

Online version: http://atlasgeneticsoncology.org/haematological/1616/t(5;12)(p13;p13)