2nd International Cancer Study & Therapy Conference
Feb 20-22, 2017, Baltimore, USA
Oncogenic activity of fusion genes
University of Pittsburgh School of Medicine, USA
Accurate prediction of prostate cancer clinical courses remains elusive. In recent studies, we performed whole genome analysis on prostate cancers by combiningAffymetrix SNP6.0 chip, whole genome sequencing and transcriptome sequencing. Our result showed that combination of genome copy number variance and novel fusion transcripts specific for cancer achieved high accuracy in predicting prostate cancer outcomes. The prediction model was further improved when these molecular criteria were combined with Nomogram or Gleasonʼs grading. Interestingly, some of these fusion genes are also present in a variety of human malignancies. Treatment of cancers with drugs specific for fusion gene signaling pathways produced dramatic improvement of metastasis and survival rate of animals xenografted with cancers positive for fusion genes. Our analyses suggest that targeting therapy for fusion genes holds promise as an effective treatment for human cancers.
Dr. Luo been studying molecular pathology related to human malignancies in the last 24 years. Currently, he is a Professor of Pathology and Director of High Throughput Genome Center at University of Pittsburgh. In the last 16 years, Dr. Luo has been largely focusing on genetic and molecular mechanism of human prostate and hepatocellular carcinomas. In this period, his group has identified and characterized several genes that are related to prostate cancer and hepatocellular carcinoma, including SAPC, myopodin, CSR1, GPx3, ITGA7, MCM7, MT1h and GPC3. He has characterized several signaling pathways that play critical role in prostate cancer development, including Myopodin-ILK-MCM7 inhibitory signaling, myopodin-zyxin motility inhibition pathway, CSR1-CPSF3, CSR1-SF3A3 and CSR1-XIAP apoptotic pathways, MT1h-EHMT1 egigenomic signaling, ITGA7-HtrA2 tumor suppression pathway, GPx3-PIG3 cell death pathway, AR-MCM7 and MCM7-SF3B3 oncogenic pathways. He proposed prostate cancer field effect in 2002. He is one of the pioneers in utilizing high throughput gene expression and genome analyses to analyze field effects in prostate cancer and liver cancer. He is also the first in using methylation array and whole genome methylation sequencing to analyze prostate cancer. Recently, Dr. Luoʼs group found that patterns of copy number variants of certain specific genome loci are predictive of prostate cancer clinical outcomes, regardless tissue origin. His discovery of several novel fusion transcripts and their association with aggressive prostate cancer has brought significant new insight into the field of prostate cancer research. Overall, these findings advance our understanding onhow cancer develops and behaves, and lay down the foundation for better future diagnosis and treatment of human malignancies.