Centromere and kinetochore gene misexpression predicts cancer patient survival and response to radiotherapy and chemotherapy

Research output: Contribution to journalArticlepeer-review

Authors

  • Weiguo Zhang
  • Jian-Hua Mao
  • Wei Zhu
  • Anshu K Jain
  • Ke Liu
  • Gary H Karpen

Colleges, School and Institutes

External organisations

  • Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, One Cyclotron Road, Mailstop 977, Berkeley, California 94720, USA.
  • Department of Translational Bioinformatics, Cellular Biomedicine Group, Inc., Level 5, Building 1, 333 Guiping Road, Shanghai 200233, the People's Republic of China.
  • Yale University
  • Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, One Cyclotron Road, Mailstop 977, Berkeley, California 94720, USA.

Abstract

Chromosomal instability (CIN) is a hallmark of cancer that contributes to tumour heterogeneity and other malignant properties. Aberrant centromere and kinetochore function causes CIN through chromosome missegregation, leading to aneuploidy, rearrangements and micronucleus formation. Here we develop a Centromere and kinetochore gene Expression Score (CES) signature that quantifies the centromere and kinetochore gene misexpression in cancers. High CES values correlate with increased levels of genomic instability and several specific adverse tumour properties, and prognosticate poor patient survival for breast and lung cancers, especially early-stage tumours. They also signify high levels of genomic instability that sensitize cancer cells to additional genotoxicity. Thus, the CES signature forecasts patient response to adjuvant chemotherapy or radiotherapy. Our results demonstrate the prognostic and predictive power of the CES, suggest a role for centromere misregulation in cancer progression, and support the idea that tumours with extremely high CIN are less tolerant to specific genotoxic therapies.

Details

Original languageEnglish
Article number12619
JournalNature Communications
Volume7
Publication statusPublished - 31 Aug 2016

Keywords

  • Journal Article