In this article , which was published in the July 15, 2010 issue of Clinical Cancer Research (1), there was an error in Fig. 1 in that activating PIK3CA mutations in JIMT-1 (C420R) and MFM-223 (H1047R) were not reported. The corrected figure and legend appear here. Based on revised statistical analysis, the second sentence of the second paragraph of the Results section should read, “We found that cell lines harboring oncogenic mutations in PIK3CA, or HER2 amplification, were significantly more sensitive than cell lines without any PI3K pathway-activating biomarker (P = 0.01 PIK3CA vs. wild-type, P = 0.02 HER2 vs. wild-type, Mann–Whitney U test; Fig. 1C).” This finding does not impact the overall conclusions of the article regarding the predictive value of PIK3CA mutations in preclinical breast cancer models. We apologize to the readers for any inconvenience this omission may have caused.
In vitro response to GDC-0941 and relationship to phosphatidylinositol 3′ kinase pathway alterations and breast cancer subtype. A, the bar chart shows the half-maximal inhibitory concentration (IC50) of GDC-0941 for 54 breast cancer cell lines, determined from an ATP-based cell viability assay and ordered from lowest to highest. Boxes below the chart indicate molecular subtype (L, luminal; H, HER2-amplified; B, basal-like), activating mutations in PIK3CA (blue), HER2 amplification (green), or PTEN protein loss determined by Western blotting (red). Molecular subtype of each cell line was determined by gene expression profiling and assessing HER2 amplification status, as described previously (18, 19). The cell lines AU565 and SKBR3 are independently derived cell lines from the same HER2-positive breast cancer patient, whereas KPL-1 and MCF-7 are independently derived cell lines from the same ER-positive breast cancer patient. B, sensitivity profile of 3 different PI3K inhibitors across the breast cancer cell line panel. Cell lines in the heat map are clustered by z-score–transformed IC50 values. GDC-0941 is a pan-inhibitor of all four class I subunits of PI3K, PI3KA/D is selective for the α- and δ-subunits, and PI-103 is a dual inhibitor of Class I PI3K and mTOR. C, scatter plot showing relationship between GDC-0941 IC50 (y-axis) and genetic alterations in key signaling pathway components in the cell lines (x-axis). D, scatter plot showing relationship between GDC-0941 IC50 (y-axis) and molecular subtype of the cell lines (x-axis).
In vitro response to GDC-0941 and relationship to phosphatidylinositol 3′ kinase pathway alterations and breast cancer subtype. A, the bar chart shows the half-maximal inhibitory concentration (IC50) of GDC-0941 for 54 breast cancer cell lines, determined from an ATP-based cell viability assay and ordered from lowest to highest. Boxes below the chart indicate molecular subtype (L, luminal; H, HER2-amplified; B, basal-like), activating mutations in PIK3CA (blue), HER2 amplification (green), or PTEN protein loss determined by Western blotting (red). Molecular subtype of each cell line was determined by gene expression profiling and assessing HER2 amplification status, as described previously (18, 19). The cell lines AU565 and SKBR3 are independently derived cell lines from the same HER2-positive breast cancer patient, whereas KPL-1 and MCF-7 are independently derived cell lines from the same ER-positive breast cancer patient. B, sensitivity profile of 3 different PI3K inhibitors across the breast cancer cell line panel. Cell lines in the heat map are clustered by z-score–transformed IC50 values. GDC-0941 is a pan-inhibitor of all four class I subunits of PI3K, PI3KA/D is selective for the α- and δ-subunits, and PI-103 is a dual inhibitor of Class I PI3K and mTOR. C, scatter plot showing relationship between GDC-0941 IC50 (y-axis) and genetic alterations in key signaling pathway components in the cell lines (x-axis). D, scatter plot showing relationship between GDC-0941 IC50 (y-axis) and molecular subtype of the cell lines (x-axis).
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