The Transcriptomic Landscape of Oncogenic PI3K Reveals Key Functions in Splicing and Gene Expression Regulation

This study includes RNA-seq of paired tumor biopsies from PIK3CA-mutated breast cancer patients that underwent treatment with PI3Kα inhibitors.]]>
Patients with known PIK3CA mutations were enrolled in an open-label, phase I dose-escalation study of oral daily GDC-0077 alone (Arm A), in combination with endocrine therapy with or without palbociclib (Arm C: GDC-0077 + Letrozole; ARM D: GDC-0077 + Fulvestrant; Arm B: GDC-0077 + Letrozole + Palbociclib; Arm E: GDC-0077 + Fulvestrant + Palbociclib; Arm F: GDC-0077 + Fulvestrant + Palbociclib + Metformin prophylaxis) (NCT03006172). Patients who had consented to this multicenter trial at Memorial Sloan Kettering Cancer Center were identified to have a PIK3CA mutation using any Clinical Laboratory Improvement Amendments (CLIA)-certified assay, including our in-house next-generation sequencing (NGS) assay- MSK-IMPACT, demonstrating a hotspot mutation that was prespecified in the trial. Those who were enrolled in the trial and had not previously had MSK-IMPACT assay performed from archival tissue were in parallel consented to our in-house protocol of genomic profiling, a mechanism within the institution to retrospectively and prospectively collect data (and additional blood/tissue) generated by various molecular profiling platforms in cancer patients who might be candidates for targeted cancer therapy (MSK IRB# 12-245).]]>