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

doi:10.1073/pnas.0809242105

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

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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 language	English (US)
Pages (from-to)	18490-18495
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	105
Issue number	47
DOIs	https://doi.org/10.1073/pnas.0809242105
State	Published - Nov 25 2008

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Weichselbaum, R. R., Ishwaran, H., Yoon, T., Nuyten, D. S. A., Baker, S. W., Khodarev, N., Su, A. W., Shaikh, A. Y., Roach, P., Kreike, B., Roizman, B., Bergh, J., Pawitan, Y., Van De Vijver, M. J., & Minn, A. J. (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, 105(47), 18490-18495. https://doi.org/10.1073/pnas.0809242105

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 journal › Article

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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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.",

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