Abstract B45: Studying the interactome of breast cancer: The cancer cell map initiative

Recent progress in genome sequencing has revealed numerous mutations in cancer genomes, but how many of these alterations result in changes in normal cellular processes is poorly understood. In addition, the biologic functions of the majority of genes (e.g., BRCA1/2) with cancer-associated mutations have not been fully characterized, despite their expression and/or activity being highly correlated with cancer. Through years of study, it is becoming clear that cancer is a disease that arises not only because of defects in individual genes and proteins, but also because of the action of hallmark cellular processes and biologic pathways. Therefore, what is urgently needed is to put the cancer genomic information into biologic context by mapping mutated genes onto the complexes and pathways in which they function. The goal of this study is to uncover the comprehensive protein-protein interaction networks and pathways in various breast cancer subtypes to better understand how mutated cancer genes and genomes hijack and rewire pathways and complexes during the course of breast tumorigenesis. Here we catalog protein-protein interactions for more than 40 genes recurrently mutated in breast cancer, using affinity purification and mass spectrometry (AP-MS). Our interaction network reveals subtype and mutation-specific protein-protein interactions, most of which are not previously reported. We anticipate the breast cancer interactome study will uncover many previously unidentified aberrant pathways and protein complexes uniquely operating in breast cancer cells, and thus pinpoint proteins central in these pathways and complexes that may potentially serve as distinct biomarkers or therapeutic targets for tumors having the same or similar subtypes and/or genomic mutations. Citation Format: Minkyu Kim, Kyumin Kim, Margaret Soucheray, Danielle Swaney, Nevan Krogan. Studying the interactome of breast cancer: The cancer cell map initiative [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr B45.