NUP98-NSD1 gene fusion and its related gene expression signature are strongly associated with a poor prognosis in pediatric acute myeloid leukemia

Norio Shiba, Hitoshi Ichikawa, Tomohiko Taki, Myoung Ja Park, Aoi Jo, Sachiyo Mitani, Tohru Kobayashi, Akira Shimada, Manabu Sotomatsu, Hirokazu Arakawa, Souichi Adachi, Akio Tawa, Keizo Horibe, Masahiro Tsuchida, Ryoji Hanada, Ichiro Tsukimoto, Yasuhide Hayashi

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Abstract

The cryptic t(5;11)(q35;p15.5) creates a fusion gene between the NUP98 and NSD1 genes. To ascertain the significance of this gene fusion, we explored its frequency, clinical impact, and gene expression pattern using DNA microarray in pediatric acute myeloid leukemia (AML) patients. NUP98-NSD1 fusion transcripts were detected in 6 (4.8%) of 124 pediatric AML patients. Supervised hierarchical clustering analyses using probe sets that were differentially expressed in these patients detected a characteristic gene expression pattern, including 18 NUP98-NSD1-negative patients (NUP98-NSD1-like patients). In total, a NUP98-NSD1-related gene expression signature (NUP98-NSD1 signature) was found in 19% (24/124) and in 58% (15/26) of cytogenetically normal cases. Their 4-year overall survival (OS) and event-free survival (EFS) were poor (33.3% in NUP98-NSD1-positive and 38.9% in NUP98-NSD1-like patients) compared with 100 NUP98-NSD1 signature-negative patients (4-year OS: 86.0%, 4-year EFS: 72.0%). Interestingly, t(7;11)(p15;p15)/NUP98-HOXA13, t(6;11)(q27;q23)/MLL-MLLT4 and t(6;9)(p22;q34)/DEK-NUP214, which are known as poor prognostic markers, were found in NUP98-NSD1-like patients. Furthermore, another type of NUP98-NSD1 fusion transcript was identified by additional RT-PCR analyses using other primers in a NUP98-NSD1-like patient, revealing the significance of this signature to detect NUP98-NSD1 gene fusions and to identify a new poor prognostic subgroup in AML.

Original languageEnglish
Pages (from-to)683-693
Number of pages11
JournalGenes Chromosomes and Cancer
Volume52
Issue number7
DOIs
Publication statusPublished - Jul 2013

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Gene Fusion
Transcriptome
Acute Myeloid Leukemia
Pediatrics
nuclear pore complex protein 98
Disease-Free Survival
Gene Expression
Survival
Oligonucleotide Array Sequence Analysis
Cluster Analysis

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

NUP98-NSD1 gene fusion and its related gene expression signature are strongly associated with a poor prognosis in pediatric acute myeloid leukemia. / Shiba, Norio; Ichikawa, Hitoshi; Taki, Tomohiko; Park, Myoung Ja; Jo, Aoi; Mitani, Sachiyo; Kobayashi, Tohru; Shimada, Akira; Sotomatsu, Manabu; Arakawa, Hirokazu; Adachi, Souichi; Tawa, Akio; Horibe, Keizo; Tsuchida, Masahiro; Hanada, Ryoji; Tsukimoto, Ichiro; Hayashi, Yasuhide.

In: Genes Chromosomes and Cancer, Vol. 52, No. 7, 07.2013, p. 683-693.

Research output: Contribution to journalArticle

Shiba, N, Ichikawa, H, Taki, T, Park, MJ, Jo, A, Mitani, S, Kobayashi, T, Shimada, A, Sotomatsu, M, Arakawa, H, Adachi, S, Tawa, A, Horibe, K, Tsuchida, M, Hanada, R, Tsukimoto, I & Hayashi, Y 2013, 'NUP98-NSD1 gene fusion and its related gene expression signature are strongly associated with a poor prognosis in pediatric acute myeloid leukemia', Genes Chromosomes and Cancer, vol. 52, no. 7, pp. 683-693. https://doi.org/10.1002/gcc.22064
Shiba, Norio ; Ichikawa, Hitoshi ; Taki, Tomohiko ; Park, Myoung Ja ; Jo, Aoi ; Mitani, Sachiyo ; Kobayashi, Tohru ; Shimada, Akira ; Sotomatsu, Manabu ; Arakawa, Hirokazu ; Adachi, Souichi ; Tawa, Akio ; Horibe, Keizo ; Tsuchida, Masahiro ; Hanada, Ryoji ; Tsukimoto, Ichiro ; Hayashi, Yasuhide. / NUP98-NSD1 gene fusion and its related gene expression signature are strongly associated with a poor prognosis in pediatric acute myeloid leukemia. In: Genes Chromosomes and Cancer. 2013 ; Vol. 52, No. 7. pp. 683-693.
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abstract = "The cryptic t(5;11)(q35;p15.5) creates a fusion gene between the NUP98 and NSD1 genes. To ascertain the significance of this gene fusion, we explored its frequency, clinical impact, and gene expression pattern using DNA microarray in pediatric acute myeloid leukemia (AML) patients. NUP98-NSD1 fusion transcripts were detected in 6 (4.8{\%}) of 124 pediatric AML patients. Supervised hierarchical clustering analyses using probe sets that were differentially expressed in these patients detected a characteristic gene expression pattern, including 18 NUP98-NSD1-negative patients (NUP98-NSD1-like patients). In total, a NUP98-NSD1-related gene expression signature (NUP98-NSD1 signature) was found in 19{\%} (24/124) and in 58{\%} (15/26) of cytogenetically normal cases. Their 4-year overall survival (OS) and event-free survival (EFS) were poor (33.3{\%} in NUP98-NSD1-positive and 38.9{\%} in NUP98-NSD1-like patients) compared with 100 NUP98-NSD1 signature-negative patients (4-year OS: 86.0{\%}, 4-year EFS: 72.0{\%}). Interestingly, t(7;11)(p15;p15)/NUP98-HOXA13, t(6;11)(q27;q23)/MLL-MLLT4 and t(6;9)(p22;q34)/DEK-NUP214, which are known as poor prognostic markers, were found in NUP98-NSD1-like patients. Furthermore, another type of NUP98-NSD1 fusion transcript was identified by additional RT-PCR analyses using other primers in a NUP98-NSD1-like patient, revealing the significance of this signature to detect NUP98-NSD1 gene fusions and to identify a new poor prognostic subgroup in AML.",
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T1 - NUP98-NSD1 gene fusion and its related gene expression signature are strongly associated with a poor prognosis in pediatric acute myeloid leukemia

AU - Shiba, Norio

AU - Ichikawa, Hitoshi

AU - Taki, Tomohiko

AU - Park, Myoung Ja

AU - Jo, Aoi

AU - Mitani, Sachiyo

AU - Kobayashi, Tohru

AU - Shimada, Akira

AU - Sotomatsu, Manabu

AU - Arakawa, Hirokazu

AU - Adachi, Souichi

AU - Tawa, Akio

AU - Horibe, Keizo

AU - Tsuchida, Masahiro

AU - Hanada, Ryoji

AU - Tsukimoto, Ichiro

AU - Hayashi, Yasuhide

PY - 2013/7

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