Genomic alterations identified by array comparative genomic hybridization as prognostic markers in breast cancer recurrence
Authors: K. Hwang, W. Han, J. Lee, J. Cho, E. Ko, E. K. Kim, S. Jung, E. Jeong, J. Bae, S. Kim, D. Noh
Journal: Journal of Clinical Oncology (2008)

11105 Background: We tried to establish models to predict systemic recurrence in breast cancer through the selection of the marker clones related with systemic recurrence by the analysis of array comparative genomic hybridization (array CGH). Methods: We performed array CGH with 4,044 human bacterial artificial chromosome (BAC) clones to assess copy number changes in 31 pairs of clinicopathologically well matched recurred/nonrecurred fresh-frozen breast cancer tissues. We selected those clones that hit the conditions of frequency criteria (more than 10%), consecutive clones (more than 2 clones), chi square test (p<0.05), multiple comparison test (False Discovery Rate (FDR), adjusted p<0.05), and Kaplan-Meier test (p<0.05). Results: 14 significant clones (11 clones in gain group and 3 clones in loss group) by disease free survival (DFS) analysis and 23 significant clones (17 clones in gain group and 6 clones in loss group) by FDR analysis were selected to be the candidate clones for predictive markers of systemic breast cancer recurrence. The most significant chromosomal alterations were found in the region of 5p15.33, 11q13.3, 15q26.3, 17q25.3, 18q23, 21q22.3 in gain, and 9p12, 11q24.1, 14q32.33 in loss. We presented the prediction models for systemic recurrence of breast cancer with 14 clones by DFS analysis and 23 clones by FDR analysis and the most effective cutoff values that can differentiate recurrence and nonrecurrence group were 9 and 16, respectively. Both methods are very effective in differentiation of recurrence and nonrecurrence group in ROC (Receiver operating characteristic) curve, DFS (disease free survival) curve, and OS (overall survival) curves analysis. Conclusion: New prediction models for systemic breast cancer recurrence by array CGH are very effective in differentiation of recurrence and nonrecurrence group. Candidate clone list by DFS analysis. Gain/loss Clone No FDR* DFS† OS‡ Cytoband Kb start Kb end Gain G1 0.006 0.0091 NS§ 18q23 75560433 75675514 G2 0.003 0.0101 NS 18q23 75297452 75415757 G3 0.012 0.0108 NS 5p15.33 473194 562560 G4 0.038 0.0141 NS 11q13.3 68979948 69057580 G5 0.006 0.0156 NS 21q22.3 45569815 45705137 G6 0.007 0.0159 NS 21q22.3 45471798 45579272 G7 0.015 0.0178 NS 18q23 75349325 75445847 G8 0.025 0.0256 NS 5p15.33 1238863 1353967 G9 0.010 0.0300 NS 15q26.3 100054894 100129431 G10 0.022 0.0325 NS 21q22.3 45997499 46084397 G11 0.038 0.0402 NS 17q25.3 78397724 78495803 G12 0.006 NS NS 21q22.3 46189033 46296404 G13 0.022 NS NS 21q22.3 46373142 46463667 G14 0.028 NS NS 21q22.3 45096044 45190446 G15 0.032 NS NS 7q36.3 157949176 158051524 G16 0.034 NS NS 21q22.3 45592803 45703201 G17 0.043 NS NS 21q22.3 45750504 45902278 Loss L1 0.011 0.020 NS 11q24.1 123006292 123091777 L2 0.024 0.022 0.019 14q32.33 105821330 105907464 L3 0.026 0.039 NS 9p12 43575387 43660307 L4 0.033 NS NS 8p23.1 7323700 7428919 L5 0.043 NS NS 8p23.3 318316 432795 L6 0.044 NS NS 10q11.22 46749417 46837491 * False discovery rate; † Disease free survival; ‡ Overall survival; § not significant Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Ministry of Health & Welfare, R.O.K