TY - JOUR
T1 - Integration of Genomic Data Enables Selective Discovery of Breast Cancer Drivers
AU - Sanchez-Garcia, Félix
AU - Villagrasa, Patricia
AU - Matsui, Junji
AU - Kotliar, Dylan
AU - Castro, Verónica
AU - Akavia, Uri David
AU - Chen, Bo Juen
AU - Saucedo-Cuevas, Laura
AU - Rodriguez Barrueco, Ruth
AU - Llobet-Navas, David
AU - Silva, Jose M.
AU - Pe'Er, Dana
N1 - Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2014/12/4
Y1 - 2014/12/4
N2 - Identifying driver genes in cancer remains a crucial bottleneck in therapeutic development and basic understanding of the disease. We developed Helios, an algorithm that integrates genomic data from primary tumors with data from functional RNAi screens to pinpoint driver genes within large recurrently amplified regions of DNA. Applying Helios to breast cancer data identified a set of candidate drivers highly enriched with known drivers (p < 10-14). Nine of ten top-scoring Helios genes are known drivers of breast cancer, and in vitro validation of 12 candidates predicted by Helios found ten conferred enhanced anchorage-independent growth, demonstrating Helios's exquisite sensitivity and specificity. We extensively characterized RSF-1, a driver identified by Helios whose amplification correlates with poor prognosis, and found increased tumorigenesis and metastasis in mouse models. We have demonstrated a powerful approach for identifying driver genes and how it can yield important insights into cancer.
AB - Identifying driver genes in cancer remains a crucial bottleneck in therapeutic development and basic understanding of the disease. We developed Helios, an algorithm that integrates genomic data from primary tumors with data from functional RNAi screens to pinpoint driver genes within large recurrently amplified regions of DNA. Applying Helios to breast cancer data identified a set of candidate drivers highly enriched with known drivers (p < 10-14). Nine of ten top-scoring Helios genes are known drivers of breast cancer, and in vitro validation of 12 candidates predicted by Helios found ten conferred enhanced anchorage-independent growth, demonstrating Helios's exquisite sensitivity and specificity. We extensively characterized RSF-1, a driver identified by Helios whose amplification correlates with poor prognosis, and found increased tumorigenesis and metastasis in mouse models. We have demonstrated a powerful approach for identifying driver genes and how it can yield important insights into cancer.
UR - http://www.scopus.com/inward/record.url?scp=84925435486&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2014.10.048
DO - 10.1016/j.cell.2014.10.048
M3 - Article
C2 - 25433701
AN - SCOPUS:84925435486
SN - 0092-8674
VL - 159
SP - 1461
EP - 1475
JO - Cell
JF - Cell
IS - 6
ER -