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

Written2014-03Nathalie Douet-Guilbert, Etienne De Braekeleer, Corinne Tous, Nadia Guéganic, Audrey Basinko, Marie-Josée Le Bris, Frédéric Morel, Marc De Braekeleer
Cytogenetics Laboratory, Faculty of Medicine, University of Brest, France

(Note : for Links provided by Atlas : click)


ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
Atlas_Id 1679

Clinics and Pathology

Disease Acute monocytic leukemia (AML-M5b)
Epidemiology 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).
Clinics A 37-year-old man seen because of throat infection resistant to antibiotics, persistent fever and dyspnea.
Treatment Induction therapy and several salvage therapies failed to achieve complete remission followed by bone marrow transplantation.
Evolution Patient alive in complete remission 35 months following bone marrow transplantation.


Note 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).
Cytogenetics Morphological t(5;11)(q35;q12) is identified by banding cytogenetics.
  RHG banding showing chromosomes 5 and 11 and the derivatives der(5) and der(11).
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.
  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 NameNSD1 (Nuclear receptor-binding, su (var), enhancer-of-zeste and trithorax domain-containing protein 1
Location 5q35.2
Dna / Rna The NSD1 gene contains 24 exons, of which 23 are coding, spanning 167 kb. Two alternative transcripts are known (Kurotaki et al., 2001).
Protein 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 NameFEN1 (flap structure-specific endonuclease 1)
Location 11q12.2
Dna / Rna The FEN1 gene contains 2 exons, of which a sole is coding, spanning 4 kb (Hiraoka et al., 1995).
Protein 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).

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.


Flap endonuclease 1: a novel tumour suppresser protein.
Henneke G, Friedrich-Heineken E, Hubscher U.
Trends Biochem Sci. 2003 Jul;28(7):384-90. (REVIEW)
PMID 12878006
Sequence of human FEN-1, a structure-specific endonuclease, and chromosomal localization of the gene (FEN1) in mouse and human.
Hiraoka LR, Harrington JJ, Gerhard DS, Lieber MR, Hsieh CL.
Genomics. 1995 Jan 1;25(1):220-5.
PMID 7774922
Two distinct nuclear receptor interaction domains in NSD1, a novel SET protein that exhibits characteristics of both corepressors and coactivators.
Huang N, vom Baur E, Garnier JM, Lerouge T, Vonesch JL, Lutz Y, Chambon P, Losson R.
EMBO J. 1998 Jun 15;17(12):3398-412.
PMID 9628876
Acute myeloid leukemia with t(5;11): two case reports.
Itoh M, Okazaki T, Tashima M, Sawada H, Uchiyama T.
Leuk Res. 1999 Jul;23(7):677-80.
PMID 10400190
A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood acute myeloid leukemia.
Jaju RJ, Fidler C, Haas OA, Strickson AJ, Watkins F, Clark K, Cross NC, Cheng JF, Aplan PD, Kearney L, Boultwood J, Wainscoat JS.
Blood. 2001 Aug 15;98(4):1264-7.
PMID 11493482
Molecular characterization of NSD1, a human homologue of the mouse Nsd1 gene.
Kurotaki N, Harada N, Yoshiura K, Sugano S, Niikawa N, Matsumoto N.
Gene. 2001 Nov 28;279(2):197-204.
PMID 11733144
Cytogenetic study of 130 childhood acute nonlymphocytic leukemias.
Leverger G, Bernheim A, Daniel MT, Flandrin G, Schaison G, Berger R.
Med Pediatr Oncol. 1988;16(4):227-32.
PMID 3419390
Flap endonuclease 1 contributes to telomere stability.
Saharia A, Guittat L, Crocker S, Lim A, Steffen M, Kulkarni S, Stewart SA.
Curr Biol. 2008 Apr 8;18(7):496-500. doi: 10.1016/j.cub.2008.02.071.
PMID 18394896
Human flap endonuclease structures, DNA double-base flipping, and a unified understanding of the FEN1 superfamily.
Tsutakawa SE, Classen S, Chapados BR, Arvai AS, Finger LD, Guenther G, Tomlinson CG, Thompson P, Sarker AH, Shen B, Cooper PK, Grasby JA, Tainer JA.
Cell. 2011 Apr 15;145(2):198-211. doi: 10.1016/j.cell.2011.03.004.
PMID 21496641
Translocation between chromosome 5q35 and chromosome 11q13-- an unusual cytogenetic finding in a primary refractory acute myeloid leukemia.
Wang TF, Horsley SW, Lee KF, Chu SC, Li CC, Kao RH.
Clin Lab Haematol. 2006 Jun;28(3):160-3.
PMID 16706931
Functional regulation of FEN1 nuclease and its link to cancer.
Zheng L, Jia J, Finger LD, Guo Z, Zer C, Shen B.
Nucleic Acids Res. 2011 Feb;39(3):781-94. doi: 10.1093/nar/gkq884. Epub 2010 Oct 6. (REVIEW)
PMID 20929870
Acute myeloid leukemia (AML-M2) with t(5;11)(q35;q13) and normal expression of cyclin D1.
de Oliveira FM, Tone LG, Simoes BP, Falcao RP, Brassesco MS, Sakamoto-Hojo ET, dos Santos GA, Marinato AF, Jacomo RH, Rego EM.
Cancer Genet Cytogenet. 2007 Jan 15;172(2):154-7.
PMID 17213025


This paper should be referenced as such :
N Douet-Guilbert, Braekeleer E De, C Tous, N Guéganic, A Basinko, Bris MJ Le, F Morel, Braekeleer M De
t(5;11)(q35;q12) NSD1/FEN1
Atlas Genet Cytogenet Oncol Haematol. 2014;18(11):853-855.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Translocations implicated (Data extracted from papers in the Atlas)

 t(5;11)(q35;q12) NSD1/FEN1

External links

Mitelman databaset(5;11)(q35;q12)
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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