An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer

Ralph R. Weichselbaum, Hemant Ishwaran, Taewon Yoon, Dimitry S A Nuyten, Samuel W. Baker, Nikolai Khodarev, Andy W. Su, Arif Y. Shaikh, Paul Roach, Bas Kreike, Bernard Roizman, Jonas Bergh, Yudi Pawitan, Marc J. Van De Vijver, Andy J. Minn

Research output: Contribution to journalArticle

247 Citations (Scopus)

Abstract

Individualization of cancer management requires prognostic markers and therapy-predictive markers. Prognostic markers assess risk of disease progression independent of therapy, whereas therapy-predictive markers identify patients whose disease is sensitive or resistant to treatment. We show that an experimentally derived IFN-related DNA damage resistance signature (IRDS) is associated with resistance to chemotherapy and/or radiation across different cancer cell lines. The IRDS genes STAT1, ISG15, and IFIT1 all mediate experimental resistance. Clinical analyses reveal that IRDS(+) and IRDS(-) states exist among common human cancers. In breast cancer, a seven-gene-pair classifier predicts for efficacy of adjuvant chemotherapy and for local-regional control after radiation. By providing information on treatment sensitivity or resistance, the IRDS improves outcome prediction when combined with standard markers, risk groups, or other genomic classifiers.

Original languageEnglish
Pages (from-to)18490-18495
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number47
DOIs
StatePublished - Nov 25 2008
Externally publishedYes

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Interferons
DNA Damage
Radiation
Breast Neoplasms
Drug Therapy
Genes
Therapeutics
Neoplasms
Adjuvant Chemotherapy
Disease Progression
Cell Line

ASJC Scopus subject areas

  • General

Cite this

An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer. / Weichselbaum, Ralph R.; Ishwaran, Hemant; Yoon, Taewon; Nuyten, Dimitry S A; Baker, Samuel W.; Khodarev, Nikolai; Su, Andy W.; Shaikh, Arif Y.; Roach, Paul; Kreike, Bas; Roizman, Bernard; Bergh, Jonas; Pawitan, Yudi; Van De Vijver, Marc J.; Minn, Andy J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 47, 25.11.2008, p. 18490-18495.

Research output: Contribution to journalArticle

Weichselbaum, RR, Ishwaran, H, Yoon, T, Nuyten, DSA, Baker, SW, Khodarev, N, Su, AW, Shaikh, AY, Roach, P, Kreike, B, Roizman, B, Bergh, J, Pawitan, Y, Van De Vijver, MJ & Minn, AJ 2008, 'An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer', Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 47, pp. 18490-18495. https://doi.org/10.1073/pnas.0809242105
Weichselbaum, Ralph R. ; Ishwaran, Hemant ; Yoon, Taewon ; Nuyten, Dimitry S A ; Baker, Samuel W. ; Khodarev, Nikolai ; Su, Andy W. ; Shaikh, Arif Y. ; Roach, Paul ; Kreike, Bas ; Roizman, Bernard ; Bergh, Jonas ; Pawitan, Yudi ; Van De Vijver, Marc J. ; Minn, Andy J. / An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 47. pp. 18490-18495.
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