NUP98

Overview

NUP98 (Nucleoporin 98) is a component of the nuclear pore complex. NUP98 is an oncogenic fusion partner in hematologic malignancies, with over 30 described partners. The NUP98–NSD1 fusion is among the most clinically significant, activating HOXA gene expression and driving AML. NUP98 fusions are typically associated with poor prognosis and chemotherapy resistance.

Alterations observed in the corpus

  • NUP98–NSD1 recurrent in-frame fusion detected by RNA-seq in adult de novo AML; identified among the recurrent in-frame fusions beyond the major known fusions (PML–RARA, MYH11–CBFB, RUNX1–RUNX1T1, BCR–ABL1) in the TCGA 200-case AML cohort PMID:23634996
  • NUP98–NSD1 fusion in pediatric AML; DOT1L-inhibitor target identified in a pediatric precision-oncology cohort PMID:28007021
  • Driver gene in the NUP98-NSD1 fusion, a classic leukemic fusion recovered in LAML fusion-only tumors in pan-cancer RNA-seq fusion analysis across 9,624 TCGA samples. PMID:29617662

Cancer types (linked)

  • AML (Acute Myeloid Leukemia): NUP98–NSD1 confirmed in the TCGA adult AML cohort (200 cases); fusion frequency not individually enumerated in the paper beyond inclusion in the list of recurrent in-frame events PMID:23634996

Co-occurrence and mutual exclusivity

  • Co-mutation patterns for NUP98–NSD1 specifically not reported in this study beyond the general finding that MLL (KMT2A) fusions (which share mechanistic parallels) had the fewest cooperating mutations PMID:23634996

Therapeutic relevance

  • NUP98–NSD1 AML has adverse prognosis; NSD1’s H3K36 methyltransferase activity and the consequent HOXA gene activation are potential therapeutic targets PMID:23634996

Open questions

  • The exact frequency of NUP98–NSD1 in this adult AML cohort and cooperating mutation profile require further characterization; this fusion is more commonly described in pediatric AML PMID:23634996

Sources

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