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Transcript
Supplemental Figure Legends
Supplemental Figure S1. Flowchart depicting the normalization of SUM149 arrays to account
for scanner differences.
Supplemental Figure S2. Normalization of SUM149 arrays from GenePix platform to Agilent
platform. The difference between Agilent (black) arrays and GenePix (pink) arrays for
Carboplatin and Carboplatin+ABT888 treated tumors was used to adjust the GenePix arrays.
Principle component analysis (A) before normalization and (B) after normalization are shown.
Supplemental Figure S3. Diagram of each dataset’s analysis to arrive at the consensus list of
38 commonly regulated genes among SUM149 and MDA-MB-436 Carboplatin treatment.
Supplemental Figure S4. Scaling of arrays for BRCA-mut models.
Arrays (A) before scaling demonstrate substantial heterogeneity between SUM149 (yellow) and
MDA-MB-436 (purple) arrays. (B) After scaling, similar dynamic ranges of arrays have been
achieved.
Supplemental Figure S5. Lack of efficacy for Carboplatin with or without ABT888 in BRCA
wild-type intracranial models of TNBC. Animals in both models were treated with PBS (control),
Carboplatin 50mg/kg/week (IP), ABT888 25mg/kg/day (OG) or combination
Carboplatin+ABT888 (doses as in single agent therapy). (A) Median survival of MDA-MB468
basal-like intracranial TNBC model. Treatment started on day 14 after intracranial implantation.
(B) Median survival of MDA-MB231BR intracranial model. Treatment started on day 7 after
intracranial implantation due to the aggressive nature of this model.
Supplemental Figure S6. Representative figure of cC3 IHC staining of BRCA-wild-type
intracranial model MDA-MB-468, as quantified in Figure 4B.
Supplemental Figure S7. Gene expression patterns within BRCA-mut TNBC intracranial
tumors SUM149 (yellow) and MDA-MB-436 (purple) with control (black), ABT888 (green),
Carboplatin (red), or Carboplatin+ABT888 (blue) treatment.
Unsupervised clustering of all arrays with genes at least 80% present and a standard deviation
of 1.0 found in at least 2 samples was clustered on centroid linkage.
Supplemental Figure S8. Carboplatin-specific gene changes.
Supervised clustering of each model with genes significantly altered with Carboplatin treatment
relative to control according to Significance Analysis of Microarrays (SAM). (A) Supervised
SUM149 arrays clustered with the 176 genes differentially expressed genes with Carboplatin
treatment. (B) MDA-MB-436 tumors clustered with 5125 genes altered with Carboplatin
treatment. Carboplatin (red), Carboplatin+ABT888 (blue), ABT888 (green), and control (black)
arrays.
Supplemental Figure S9. Defining common Carboplatin response genes in BRCA-mutant
TNBC intracranial tumors.
Following identification of genes significantly altered in response to Carboplatin treatment, those
genes with fold changes >1 are considered “up-regulated”, and those <1 are “down regulated”.
(A) Overlap of genes with >1 fold change in SUM149 (yellow) and MDA-MB-436 (purple)
models defines 37 commonly up-regulated genes. (B) Overlap of genes with < 1 fold change in
SUM149 and MDA-MB-436 models defines 1 gene commonly down-regulated. (C) Fold
changes of Carboplatin treated tumors relative to control tumors across the 38 shared genes
with significantly different expression.