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


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.

SUBMITTER: Weichselbaum RR 

PROVIDER: S-EPMC2587578 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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

Weichselbaum Ralph R RR   Ishwaran Hemant H   Yoon Taewon T   Nuyten Dimitry S A DS   Baker Samuel W SW   Khodarev Nikolai N   Su Andy W AW   Shaikh Arif Y AY   Roach Paul P   Kreike Bas B   Roizman Bernard B   Bergh Jonas J   Pawitan Yudi Y   van de Vijver Marc J MJ   Minn Andy J AJ  

Proceedings of the National Academy of Sciences of the United States of America 20081110 47


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  ...[more]

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