BUB1B

Overview

BUB1B (BUB1 Mitotic Checkpoint Serine/Threonine Kinase B, also known as BUBR1) encodes a key component of the spindle assembly checkpoint (SAC), which monitors kinetochore-microtubule attachment and prevents premature anaphase onset. Germline loss-of-function mutations cause mosaic variegated aneuploidy (MVA) syndrome. In cancer, BUB1B mutations or reduced expression contribute to chromosomal instability.

Alterations observed in the corpus

  • Low-frequency (1%) mitotic-checkpoint/cell-cycle hit in pediatric rhabdomyosarcoma (RMS); identified alongside CCND1, CCND2, and FOXM1 as mitotic-checkpoint/cell-cycle gene-group alterations in a comprehensive genomic landscape study of 258 RMS samples PMID:24436047

Cancer types (linked)

  • Rhabdomyosarcoma (RMS): somatic alteration in ~1% of cases; part of the mitotic-checkpoint gene group; predominantly in PAX-fusion-negative RMS based on the study’s overall cohort composition PMID:24436047

Co-occurrence and mutual exclusivity

  • Part of the mitotic-checkpoint/cell-cycle gene group with CCND1, CCND2, and FOXM1 in RMS; broader context of low overall mutation rate (~0.1 protein-coding changes/Mb) in pediatric solid tumors PMID:24436047

Therapeutic relevance

  • No targeted therapy data specific to BUB1B-mutant RMS. BUB1B loss-of-function promotes chromosomal instability and may sensitize tumors to agents targeting aberrant mitosis PMID:24436047

Open questions

  • The low frequency (1%) limits statistical power to determine whether BUB1B mutations are true drivers or passengers in RMS; functional studies in pediatric sarcoma models are lacking PMID:24436047

Sources

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