Copy number alterations that predict metastatic capability of human breast cancer. Export

@article{ZhangFoekens2009, abstract = {We have analyzed the DNA copy numbers for over 100,000 single-nucleotide polymorphism loci across the human genome in genomic DNA from 313 lymph node-negative primary breast tumors for which genome-wide gene expression data were also available. Combining these two data sets allowed us to identify the genomic loci and their mapped genes, having high correlation with distant metastasis. An estimation of the likely response based on published predictive signatures was performed in the identified prognostic subgroups defined by gene expression and DNA copy number data. In the training set of 200 patients, we constructed an 81-gene prognostic copy number signature (CNS) that identified a subgroup of patients with increased probability of distant metastasis in the independent validation set of 113 patients [hazard ratio (HR), 2.8; 95\% confidence interval (95\% CI), 1.4-5.6] and in an external data set of 116 patients (HR, 3.7; 95\% CI, 1.3-10.6). These high-risk patients constituted a subset of the high-risk patients predicted by our previously established 76-gene gene expression signature (GES). This very poor prognostic group identified by CNS and GES was putatively more resistant to preoperative paclitaxel and 5-fluorouracil-doxorubicin-cyclophosphamide combination chemotherapy (P = 0.0048), particularly against the doxorubicin compound, while potentially benefiting from etoposide. Our study shows the feasibility of using copy number alterations to predict patient prognostic outcome. When combined with gene expression-based signatures for prognosis, the CNS refines risk classification and can help identify those breast cancer patients who have a significantly worse outlook in prognosis and a potential differential response to chemotherapeutic drugs.}, author = {Zhang, Yi and Martens, John W. and Yu, Jack X. and Jiang, John and Sieuwerts, Anieta M. and Smid, Marcel and Klijn, Jan G. and Wang, Yixin and Foekens, John A.}, citeulike-article-id = {4257637}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/0008-5472.CAN-08-4596}, citeulike-linkout-1 = {http://cancerres.aacrjournals.org/content/69/9/3795.abstract}, citeulike-linkout-2 = {http://cancerres.aacrjournals.org/content/69/9/3795.full.pdf}, citeulike-linkout-3 = {http://cancerres.aacrjournals.org/cgi/content/abstract/69/9/3795}, citeulike-linkout-4 = {http://view.ncbi.nlm.nih.gov/pubmed/19336569}, citeulike-linkout-5 = {http://www.hubmed.org/display.cgi?uids=19336569}, day = {1}, doi = {10.1158/0008-5472.CAN-08-4596}, issn = {1538-7445}, journal = {Cancer research}, keywords = {breast\_cancer, copy\_number}, month = {May}, number = {9}, pages = {3795--3801}, posted-at = {2009-10-10 11:38:00}, priority = {2}, title = {Copy number alterations that predict metastatic capability of human breast cancer.}, url = {http://dx.doi.org/10.1158/0008-5472.CAN-08-4596}, volume = {69}, year = {2009} }

TY - JOUR ID - ZhangFoekens2009 L3 - citeulike-article-id:4257637 N2 - We have analyzed the DNA copy numbers for over 100,000 single-nucleotide polymorphism loci across the human genome in genomic DNA from 313 lymph node-negative primary breast tumors for which genome-wide gene expression data were also available. Combining these two data sets allowed us to identify the genomic loci and their mapped genes, having high correlation with distant metastasis. An estimation of the likely response based on published predictive signatures was performed in the identified prognostic subgroups defined by gene expression and DNA copy number data. In the training set of 200 patients, we constructed an 81-gene prognostic copy number signature (CNS) that identified a subgroup of patients with increased probability of distant metastasis in the independent validation set of 113 patients [hazard ratio (HR), 2.8; 95% confidence interval (95% CI), 1.4-5.6] and in an external data set of 116 patients (HR, 3.7; 95% CI, 1.3-10.6). These high-risk patients constituted a subset of the high-risk patients predicted by our previously established 76-gene gene expression signature (GES). This very poor prognostic group identified by CNS and GES was putatively more resistant to preoperative paclitaxel and 5-fluorouracil-doxorubicin-cyclophosphamide combination chemotherapy (P = 0.0048), particularly against the doxorubicin compound, while potentially benefiting from etoposide. Our study shows the feasibility of using copy number alterations to predict patient prognostic outcome. When combined with gene expression-based signatures for prognosis, the CNS refines risk classification and can help identify those breast cancer patients who have a significantly worse outlook in prognosis and a potential differential response to chemotherapeutic drugs. IS - 9 JF - Cancer research SN - 1538-7445 EP - 3801 TI - Copy number alterations that predict metastatic capability of human breast cancer. VL - 69 SP - 3795 KW - breast_cancer KW - copy_number AU - Zhang, Yi AU - Martens, John AU - Yu, Jack AU - Jiang, John AU - Sieuwerts, Anieta AU - Smid, Marcel AU - Klijn, Jan AU - Wang, Yixin AU - Foekens, John PY - 2009/05/01/ UR - http://dx.doi.org/10.1158/0008-5472.CAN-08-4596 ER -