a precisely regulated gene expression cassette potently modulates metastasis and survival in multiple solid cancers精确调控的基因表达盒有说服力地调节在多个固体癌症转移和生存.pdfVIP
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a precisely regulated gene expression cassette potently modulates metastasis and survival in multiple solid cancers精确调控的基因表达盒有说服力地调节在多个固体癌症转移和生存
A Precisely Regulated Gene Expression Cassette Potently
Modulates Metastasis and Survival in Multiple Solid
Cancers
1,2 1 3 2 1 4
Kun Yu , Kumaresan Ganesan , Lay Keng Tan , Mirtha Laban , Jeanie Wu , Xiao Dong Zhao , Hongmin
2 2 1 4 2 4
Li , Carol Ho Wing Leung , Yansong Zhu , Chia Lin Wei , Shing Chuan Hooi , Lance Miller , Patrick
Tan1,3,4*
1 National Cancer Centre, Singapore, Singapore, 2 Department of Physiology, National University of Singapore, Singapore, Singapore, 3 Duke–NUS Graduate Medical
School, Singapore, Singapore, 4 Genome Institute of Singapore, Singapore, Singapore
Abstract
Successful tumor development and progression involves the complex interplay of both pro- and anti-oncogenic signaling
pathways. Genetic components balancing these opposing activities are likely to require tight regulation, because even
subtle alterations in their expression may disrupt this balance with major consequences for various cancer-associated
phenotypes. Here, we describe a cassette of cancer-specific genes exhibiting precise transcriptional control in solid tumors.
Mining a database of tumor gene expression profiles from six different tissues, we identified 48 genes exhibiting highly
restricted levels of gene expression variation in tumors (n = 270) compared to nonmalignant tissues (n = 71). Comprising
genes linked to multiple cancer-related pathways, the restricted expression of this ‘‘Poised Gene Cassette’’ (PGC) was
robustly validated across 11 independent cohorts of ,1,300 samples from multiple cancer types. In three separate
expe
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