t(5;11)(q35;q12) NSD1/FEN1

2014-03-01   Etienne De Braekeleer , Corinne Tous , Nadia Guéganic , Audrey Basinko , Marie-Josée Le Bris , Frédéric Morel , Marc De Braekeleer , Nathalie Douet-Guilbert 

1.Cytogenetics Laboratory, Faculty of Medicine, University of Brest, France

Clinics and Pathology



Four cases of acute myeloid leukemia with t(5;11)(q35;q12-13) are reported in the literature: two acute myeloblastic leukemia with differentiation (AML-M2) (Wang et al., 2006; de Oliveira et al., 2007), one acute myelomonocytic leukemia (AML-M4) (Itoh et al., 1999) and one acute monoblastic leukemia (AML-M5) (Leverger et al., 1988). No molecular characterization was performed in these cases but the NSD1 gene was shown not to be involved by fluorescent in situ hybridization in the AML-M2 case reported by Wang et al. (2006).


A 37-year-old man seen because of throat infection resistant to antibiotics, persistent fever and dyspnea.


Induction therapy and several salvage therapies failed to achieve complete remission followed by bone marrow transplantation.


Patient alive in complete remission 35 months following bone marrow transplantation.



The t(5;11)(q35;q12) involves two genes of which one, the NSD1 gene, has been already shown to form a fusion gene with NUP98 in the t(5;11)(q35;p15.1) (Jaju et al., 2001).
Atlas Image
RHG banding showing chromosomes 5 and 11 and the derivatives der(5) and der(11).

Cytogenetics morphological

t(5;11)(q35;q12) is identified by banding cytogenetics.

Cytogenetics molecular

To determine the position of the breakpoints on chromosomes 5 and 11, BACs located in the bands of interest were used as probes in FISH experiments. Analysis with RP11-99N22 showed that one signal hybridized to the normal chromosome 5, and the other split and hybridized to both der(5) and der(11). FISH with overlapping BACs identified a very small region of breakage in RP11-467L20. Analysis with RP11-467L20 showed that one signal hybridized to the normal chromosome 11, and the other split and hybridized to both der(11) and der(5). Co-hybridization with both BAC clones showed two fusion signals. RP11-99N22 contains the NSD1 gene and RP11-467L20 the FEN1 gene.
Atlas Image
FISH with BACs RP11-99N22 (spectrum orange, located in 5q35 and containing NSD1) and RP11-467L20 (spectrum green, located in 11q12 and containing FEN1) showing co-hybridization.

Genes Involved and Proteins

Gene name
NSD1 (Nuclear receptor-binding, su (var), enhancer-of-zeste and trithorax domain-containing protein 1
Dna rna description
The NSD1 gene contains 24 exons, of which 23 are coding, spanning 167 kb. Two alternative transcripts are known (Kurotaki et al., 2001).
Protein description
The protein has 2696 amino acids and localizes to the nucleus. It contains a SET domain, 2 LXXLL motifs, 3 nuclear translocation signals, 4 plant homeodomain (PHD) finger regions, and a proline-rich region. The protein acts as a basic transcriptional factor and also as a bifunctional transcriptional regulator, capable of both negatively or positively influencing transcription, depending on the cellular context (Huang et al., 1998; Kurotaki et al., 2001).
Gene name
FEN1 (flap structure-specific endonuclease 1)
Dna rna description
The FEN1 gene contains 2 exons, of which a sole is coding, spanning 4 kb (Hiraoka et al., 1995).
Protein description
The protein has 380 amino acids and localizes to the nucleus. It is a structure-specific nuclease with 5-flap endonuclease and 5-3 exonuclease activities involved in DNA replication and repair. It acts as a genome stabilization factor that prevents flaps from equilibrating into structures that lead to duplications and deletions and participates in telomere maintenance (Saharia et al., 2008; Zheng et al., 2011; Tsutakawa et al., 2011). It has been suggested that FEN1 is a tumor suppressor gene (Henneke et al., 2003).


Pubmed IDLast YearTitleAuthors
128780062003Flap endonuclease 1: a novel tumour suppresser protein.Henneke G et al
77749221995Sequence of human FEN-1, a structure-specific endonuclease, and chromosomal localization of the gene (FEN1) in mouse and human.Hiraoka LR et al
96288761998Two distinct nuclear receptor interaction domains in NSD1, a novel SET protein that exhibits characteristics of both corepressors and coactivators.Huang N et al
104001901999Acute myeloid leukemia with t(5;11): two case reports.Itoh M et al
114934822001A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood acute myeloid leukemia.Jaju RJ et al
117331442001Molecular characterization of NSD1, a human homologue of the mouse Nsd1 gene.Kurotaki N et al
34193901988Cytogenetic study of 130 childhood acute nonlymphocytic leukemias.Leverger G et al
183948962008Flap endonuclease 1 contributes to telomere stability.Saharia A et al
214966412011Human flap endonuclease structures, DNA double-base flipping, and a unified understanding of the FEN1 superfamily.Tsutakawa SE et al
167069312006Translocation between chromosome 5q35 and chromosome 11q13-- an unusual cytogenetic finding in a primary refractory acute myeloid leukemia.Wang TF et al
209298702011Functional regulation of FEN1 nuclease and its link to cancer.Zheng L et al
172130252007Acute myeloid leukemia (AML-M2) with t(5;11)(q35;q13) and normal expression of cyclin D1.de Oliveira FM et al


Etienne De Braekeleer ; Corinne Tous ; Nadia Guéganic ; Audrey Basinko ; Marie-Josée Le Bris ; Frédéric Morel ; Marc De Braekeleer ; Nathalie Douet-Guilbert

t(5;11)(q35;q12) NSD1/FEN1

Atlas Genet Cytogenet Oncol Haematol. 2014-03-01

Online version: http://atlasgeneticsoncology.org/haematological/1679/t(5;11)(q35;q12)