Table 3.
Selected copy number imbalances predicting breast cancer bone or non-bone metastasis, from the CoxBoost analysis
| CNI marker | Start (Mp) | Stop (Mp) | Size (Mb) | Discovery dataset
|
Validation dataset
|
Potential target genes# | ||
|---|---|---|---|---|---|---|---|---|
| HR (95% CI) | P value | HR (95% CI) | P value | |||||
| Bone metastasis | ||||||||
| 1p13.3 loss* | 107.2 | 107.8 | 0.6 | 3.54 (1.82–6.89) | 0.0002 | 2.74 (0.82–9.17) | 0.1021 | PRMT6 |
| 1q41 gain* | 212.6 | 213 | 0.4 | 2.58 (1.63–4.09) | 5.39 × 10−5 | 0.89 (0.39–2.05) | 0.7866 | PTPN14 (associated with metastasis) |
| 1q42.12 gain | 223.9 | 224.4 | 0.5 | 2.77 (1.74–4.41) | 1.64 × 10−5 | 1.28 (0.58–2.78) | 0.5415 | EPHX |
| 8p22 loss | 16.9 | 17.2 | 0.3 | 2.90 (1.75–4.82) | 3.57 × 10−5 | 2.27 (1.01–5.12) | 0.0481 | REAM (associated with metastasis), DLC1 (predictor of bone metastasis) |
| 11q13.5 gain | 76.2 | 76.7 | 0.5 | 3.11 (1.79–5.40) | 6.09 × 10−5 | 2.79 (1.11–46.99) | 0.0291 | OMP (close to metastasis genes EMSY and LRRC32) |
| Xp11.3 loss | 45.9 | 46.8 | 0.9 | 4.36 (2.30–8.28) | 6.75 × 10−6 | 1.49 (0.20–11.04) | 0.6951 | |
|
| ||||||||
| Non-bone metastasis | ||||||||
| 2p11.2 gain | 84.4 | 84.8 | 0.4 | 3.19 (1.56–6.52) | 0.0015 | 4.03 (0.98–16.63) | 0.0541 | SUCLG1 |
| 3q21.3–22.2 gain* | 127.9 | 137.4 | 9.4 | 2.89 (1.56–5.37) | 0.0008 | 1.53 (0.37–6.32) | 0.5542 | EPHB1 (associated with metastasis) |
| 3q27.1 gain | 184.7 | 185.1 | 0.4 | 2.53 (1.55–4.11) | 0.0002 | 0.20 (0.03–1.45) | 0.1109 | PARL |
| 7q21.11 loss* | 77.6 | 77.9 | 0.3 | 3.87 (1.70–8.79) | 0.0012 | 0.98 (0.24–4.02) | 0.9747 | MGC34774 |
| 10q23.1 gain | 82.2 | 82.9 | 0.6 | 3.13 (1.68–5.80) | 0.0003 | 6.39 (2.86–14.27) | 5.97 × 10−6 | SH2D4B |
| 11q13.5 gain | 75.7 | 76.2 | 0.5 | 2.32 (1.41–3.82) | 0.0010 | 2.51 (1.25–5.04) | 0.0098 | EMSY (associated with prognosis in breast and ovarian cancers); LRRC32 (associated with metastasis) |
| 14q13.2-3 gain | 35.3 | 36.2 | 0.9 | 2.54 (1.43–4.51) | 0.0014 | 2.68 (0.96–7.51) | 0.0599 | PAX9 |
Abbreviations: CNI, copy number imbalance; HR, hazard ratio; CI, confidence interval.
#
Only selected genes with biological plausibility are shown in the table. The full list of genes for each region is given in Supplemental Table 1.
*
CNI markers identified in this study. The other markers (chromosome region) listed have been previously implicated in predicting poor clinical outcome in breast cancer patients.