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

Weiguo Zhang (), Jian-Hua Mao, Wei Zhu, Anshu K. Jain, Ke Liu, James B. Brown and Gary H. Karpen ()
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Weiguo Zhang: Lawrence Berkeley National Laboratory
Jian-Hua Mao: Lawrence Berkeley National Laboratory
Wei Zhu: Cellular Biomedicine Group, Inc.
Anshu K. Jain: Yale School of Medicine, Yale University
Ke Liu: Lawrence Berkeley National Laboratory
James B. Brown: Lawrence Berkeley National Laboratory
Gary H. Karpen: Lawrence Berkeley National Laboratory

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms12619

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