NUP98-NSD3 fusion gene in radiation-associated myelodysplastic syndrome with t(8;11)(p11;p15) and expression pattern of NSD family genes.
Chromosomal 11p15 abnormality of therapy-related myelodysplastic syndrome (t-MDS)-acute myeloid leukemia (AML) is rare. NUP98-NSD3 fusion transcripts have been detected previously in one patient with AML and one patient with t-MDS having t(8;11)(p11;p15). Here we present the case of a 60-year-old man with radiation-associated MDS (r-MDS) carrying chromosome abnormalities, including t(8;11)(p11;p15) and del(1)(p22p32). Fluorescence in situ hybridization analysis demonstrated that the NUP98 gene at 11p15 was split by the translocation. Southern blot analysis of bone marrow cells showed both rearrangements of NUP98 and NSD3 genes. Reverse transcriptase-polymerase chain reaction (RT-PCR) followed by sequence analysis revealed the presence of both NUP98-NSD3 and NSD3-NUP98 fusion transcripts. Expression analysis by RT-PCR showed that NSD3 as well as NSD1 and NSD2 was ubiquitously expressed in leukemic cell lines and Epstein-Barr virus transformed B lymphocyte cell lines derived from the normal adult lymphocytes examined. Two isoforms of NSD3, NSD3S and NSD3L (but not NSD3L2), were expressed in leukemic cell lines and were fused to NUP98 in our patient, suggesting that qualitative change of these two isoforms of NSD3 by fusion with NUP98 might be related to leukemogenesis, although the function of each isoform of the NSD3 gene remains unclear.
Taketani
Takeshi
T
Division of Blood Transfusion, Shimane University Hospital, Izumo, Shimane, Japan.
Taki
Tomohiko
T
Nakamura
Hideo
H
Taniwaki
Masafumi
M
Masuda
Junichi
J
Hayashi
Yasuhide
Y
D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005786:Gene Expression Regulation; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D014178:Translocation, Genetic
C541493:NUP98-NSD3 fusion protein, human; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; C465451:Nup98 protein, human; D015514:Oncogene Proteins, Fusion; D011495:Histone-Lysine N-Methyltransferase; C432968:NSD3 protein, human