FBXW7 and DNA copy number instability

Kristin N. Byrd, Bing Huey, Ritu Roydasgupta, Jane Fridlyand, Antoine M. Snijders, Donna G. Albertson

Research output: Contribution to journalArticle

Abstract

SKP1-cullin-F-box protein (SCF) type ubiquitin ligases degrade proteins controlling the G1/S transition. Deficiency for FBXW7 (also known as hCDC4), which encodes the F-box protein of the SCF type ubiquitin ligase is associated with genomic instability. Here, we investigated the association of FBXW7 deficiency with chromosomal instability in breast cancer. We screened 49 tumors previously profiled by array CGH for mutations in conserved regions of FBXW7, but found no mutations. Copy number loss of FBXW7, however was associated with enhanced genomic instability in the Complex breast tumor subtype, but instability may not be due to FBXW7 haploinsufficiency, since transcript levels were not reduced in tumors with loss of the locus, whereas reduced expression was observed for other neighboring genes involved in maintenance of genome stability. We also investigated whether cells deficient for FBXW7 showed enhanced instability by challenging cells with methotrexate and assessing numbers of genomic alterations arising in resistant cells. Although methotrexate resistant colonies formed at high frequencies in HCT116 FBXW7+/- and HCT116 FBXW7-/- cells compared to parental HCT116, few copy number alterations were detected in the resistant cells. Taken together these studies suggest that FBXW7 deficiency is unlikely to contribute to the extensive copy number aberrations associated with breast and possibly other tumor types.

Original languageEnglish (US)
Pages (from-to)47-54
Number of pages8
JournalBreast Cancer Research and Treatment
Volume109
Issue number1
DOIs
StatePublished - May 1 2008

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Keywords

  • Array CGH
  • FBXW7
  • Genome instability

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Byrd, K. N., Huey, B., Roydasgupta, R., Fridlyand, J., Snijders, A. M., & Albertson, D. G. (2008). FBXW7 and DNA copy number instability. Breast Cancer Research and Treatment, 109(1), 47-54. https://doi.org/10.1007/s10549-007-9623-7