t(11;12)(p15;q13) NUP98/HOXC11t(11;12)(p15;q13) NUP98/HOXC13

2018-06-01   Jean-Loup Huret 



Review on t(11;12)(p15;q13), with data on clinics, and the genes involved.

Clinics and Pathology


To be noted that NUP98 gene was found rearranged but HOXC genes were not tested or neither NUP98 nor HOX genes were tested in 5 cases (Roulston et al., 1998; and Kobzev et al., 2004 are identical cases), all of which were treatment-related MDS or AML (t-MDS or t-AML): a 9 mths old boy, 3 female patients aged 39 yrs, 41 yrs and 55 yrs, and one other male patient (Roulston et al., 1998; Nishiyama et al., 1999; Wong et al., 1998; Masuya et al., 2002; Kobzev et al., 2004; Schmidt-Hieber et al., 2010). Previous diseases were Hodgkins disease in 2 cases, AML and breast cancer in one case each.
As noted by La Starza et al., 2009, a NUP98-positive acute myeloid leukemia with a t(11;12)(p15;q13) can occur without HOXC cluster gene involvement.


All the 7 cases with NUP98/HOXC hybrid gene were de novo acute myeloid leukemia: one AML without maturation (M1), four AML with maturation (M2), one acute myelomonocytic leukaemia (M4) and one acute monoblastic/monocytic leukaemia (M5b).


Sex ratio was 2M/2F in HOXC11 cases and 0M/3F in HOXC13 cases; more cases are needed to determine if this discrepancy is coincidental/stochastic. Patients were aged 14, 22, 40 and 41 yrs in HOXC11 cases and 47, 57, 59 yrs in HOXC13 cases


Two cases were in complete remission (5 mths+, NA), and four cases were reported to have died (8 mths, 8mths, 19 mths, NA).

Genes Involved and Proteins

Gene name
NUP98 (nucleoporin 98 kDa)
Dna rna description
alternate splicings
Protein description
920 amino acids (aa) and other ioforms; NUP98 belongs to the nucleoporin gene family and encodes a 186 kDa precursor protein that undergoes autoproteolytic cleavage to produce a 98 kDa and 96 kDa nucleoporins. The 98 kDa nucleoporin contains a Gly-Leu-Phe-Gly (GLFG and FG) repeat in N-term, a GLEBS-like motif (which binds RAE1), and a RNA binding motif in C-term. NUP98 is involved in nuclear import/export, mitotic progression, and regulation of gene expression (Duheron and Fahrenkrog, 2015). , 330 aa; the protein localizes in the nucleus; sequence-specific transcription factor which contains a homeodomain with helix-turn-helix (HTH) motif in aa 260 to 319.
Gene name
12q13.13; Starts at 53973126 and ends at 53976419 bp from pter ( according to hg38-Dec_2013)
Dna rna description
915 nucleotids (nt), 2 exons

Protein description
304 aa; the protein localizes in the nucleus; sequence-specific transcription factor which contains a homeodomain with helix-turn-helix (HTH) motif in aa 233 to 289.
Gene name
12q13.13; Starts at 53938792 and ends at 53946544 bp from pter ( according to hg19-Feb_2009) 
HOXC13 starts 37627 nt after the end of HOXC11.
Dna rna description
993 nt, 2 exons
Protein description
Part of the Hox clusters. There is a timing mechanism to synchronize Hox gene expression during embryogenesis ("Hox clock"). HOX genes regulates the expression of genes that are implicated during embryogenesis (anterior-posterior patterning and limbs developments). HOX genes are also expressed in adult tissues (review in Deschamps and Duboule, 2017).

Result of the Chromosomal Anomaly


The NUP98 breakpoint was between exon 11 and 12 in three HOXC11 cases (Gu et al., 2003), and between exon 14 and 15 in the other HOXC11 case (Taketani et al., 2002). It was found between exon 15 and 16 in two HOXC13 cases (La Starza et al., 2003; Panagopoulos et al., 2003). The HOXC11 breakpoint was between exon 1 and 2 (Gu et al., 2003), or in exon 1 (Taketani et al., 2002). The HOXC13 breakpoint was between exon 1 and 2 (La Starza et al., 2003; Panagopoulos et al., 2003).
Atlas Image
t(11,12)(p15;q13) NUP98/HOXC genes fuses the N-term NUP98 to the C-term of HOXC11 or HOXC13. This correspond to 469 aa, 628 aa or 715 aa in the HOXC genes, retaining the FG repeats and the GLEBS-like motif, fused to 77 aa or 120 aa from HOXC genes, including the homeodomain.


fuses the N-term NUP98 to the C-term of HOXC11 or HOXC13. This correspond to 469 aa or 628 aa from NUP98 in the HOXC11 cases and 715 aa in the HOXC13 cases fused to 77 aa from HOX11 (Gu et al., 2003), or 120 aa from HOX13 (Taketani et al., 2002).

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Pubmed IDLast YearTitleAuthors
288601582017Embryonic timing, axial stem cells, chromatin dynamics, and the Hox clock.Deschamps J et al
129707872003Major form of NUP98/HOXC11 fusion in adult AML with t(11;12)(p15;q13) translocation exhibits aberrant trans-regulatory activity.Gu BW et al
153901872004Analysis of translocations that involve the NUP98 gene in patients with 11p15 chromosomal rearrangements.Kobzev YN et al
196650722009A NUP98-positive acute myeloid leukemia with a t(11;12)(p15;q13) without HOXC cluster gene involvement.La Starza R et al
119392662002Two independent clones in myelodysplastic syndrome following treatment of acute myeloid leukemia.Masuya M et al
10502319199911p15 translocations involving the NUP98 gene in childhood therapy-related acute myeloid leukemia/myelodysplastic syndrome.Nishiyama M et al
124617552003Fusion of the NUP98 gene and the homeobox gene HOXC13 in acute myeloid leukemia with t(11;12)(p15;q13).Panagopoulos I et al
97635731998CBFA2(AML1) translocations with novel partner chromosomes in myeloid leukemias: association with prior therapy.Roulston D et al
203622282010Cytogenetic studies in acute leukemia patients relapsing after allogeneic stem cell transplantation.Schmidt-Hieber M et al
121834082002Novel NUP98-HOXC11 fusion gene resulted from a chromosomal break within exon 1 of HOXC11 in acute myeloid leukemia with t(11;12)(p15;q13).Taketani T et al
196650702009Acute myeloid leukemia with NUP98-HOXC13 fusion and FLT3 internal tandem duplication mutation: case report and literature review.Tosić N et al
94065801998De novo AML with trilineage myelodysplasia and a novel t(11;12)(p15;q13).Wong KF et al


Fusion gene



t(11;12)(p15;q13) with NUP98 and HOXC11 involvement has been described in 4 cases(Taketani et al., 2002; Gu et al., 2003), and with NUP98 and HOXC13 involvement in 3 additional cases (La Starza et al., 2003; Panagopoulos et al., 2003; Tosic et al., 2009).
Atlas Image
t(11;12)(p15;q13) G- banding - Courtesy Melanie Zenger and Claudia Haferlach.


Jean-Loup Huret

t(11;12)(p15;q13) NUP98/HOXC11t(11;12)(p15;q13) NUP98/HOXC13

Atlas Genet Cytogenet Oncol Haematol. 2018-06-01

Online version: http://atlasgeneticsoncology.org/haematological/1185/t(11;12)(p15;q13)-nup98-hoxc11t(11;12)(p15;q13)-nup98-hoxc13

Historical Card

2000-02-01 t(11;12)(p15;q13) NUP98/HOXC11t(11;12)(p15;q13) NUP98/HOXC13 by  Jean-Loup Huret 


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