Figure 8

Multiple concerted disruption (MCD) analysis and its application to triple negative breast cancer. (A) Analysis of ten simulated datasets to determine the proportion of random simulations at each observed frequency of MCD. Notably, 99.7% of random simulations had a MCD frequency of 0/9, with the remaining 0.3% at 1/9. Moreover, no simulations showed a frequency ≥ 2/9. Thus, the observation of an MCD event suggests the event is likely non-random. (B) Using the knowledge database of Ingenuity Pathway Analysis, upstream and downstream components of FGFR2 were selected to assess their role in the subset of triple negative breast cancer (TNBC) cell lines. Only components which were shown to have a direct or indirect expression level relationship were selected. Of the seven components identified (four upstream and three downstream of FGFR2), one upstream and one downstream component were present in both the MDA list (Additional File 4) and MCD list (Additional File 7). Examining FGFR2 and COL1A1, while FGFR2 overexpression is not frequently associated with DNA level alteration, COL1A1 is frequently affected at DNA level. Moreover, in the five TNBC cell lines examined, four have DNA level alteration of COL1A1 and the remaining line has DNA level alteration of FGFR2.