http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Perspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics
Ding, Li,Bailey, Matthew H.,Porta-Pardo, Eduard,Thorsson, Vesteinn,Colaprico, Antonio,Bertrand, Denis,Gibbs, David L.,Weerasinghe, Amila,Huang, Kuan-lin,Tokheim, Collin,Corté,s-Ciriano, Isidro,J Elsevier 2018 Cell Vol.173 No.2
<P><B>Summary</B></P> <P>The Cancer Genome Atlas (TCGA) has catalyzed systematic characterization of diverse genomic alterations underlying human cancers. At this historic junction marking the completion of genomic characterization of over 11,000 tumors from 33 cancer types, we present our current understanding of the molecular processes governing oncogenesis. We illustrate our insights into cancer through synthesis of the findings of the TCGA PanCancer Atlas project on three facets of oncogenesis: (1) somatic driver mutations, germline pathogenic variants, and their interactions in the tumor; (2) the influence of the tumor genome and epigenome on transcriptome and proteome; and (3) the relationship between tumor and the microenvironment, including implications for drugs targeting driver events and immunotherapies. These results will anchor future characterization of rare and common tumor types, primary and relapsed tumors, and cancers across ancestry groups and will guide the deployment of clinical genomic sequencing.</P> <P><B>Highlights</B></P> <P> <UL> <LI> An overview of PanCancer Atlas analyses on oncogenic molecular processes </LI> <LI> Germline genome affects somatic genomic landscape in a pathway-dependent fashion </LI> <LI> Genome mutations impact expression, signaling, and multi-omic profiles </LI> <LI> Mutation burdens and drivers influence immune-cell composition in microenvironment </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>
Comprehensive Characterization of Cancer Driver Genes and Mutations
Bailey, Matthew H.,Tokheim, Collin,Porta-Pardo, Eduard,Sengupta, Sohini,Bertrand, Denis,Weerasinghe, Amila,Colaprico, Antonio,Wendl, Michael C.,Kim, Jaegil,Reardon, Brendan,Kwok-Shing Ng, Patrick,Jeon Elsevier 2018 Cell Vol.174 No.4
Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation
Malta, Tathiane M.,Sokolov, Artem,Gentles, Andrew J.,Burzykowski, Tomasz,Poisson, Laila,Weinstein, John N.,Kamiń,ska, Boż,ena,Huelsken, Joerg,Omberg, Larsson,Gevaert, Olivier,Colaprico, Anto Elsevier 2018 Cell Vol.173 No.2
<P><B>Summary</B></P> <P>Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation.</P> <P><B>Video Abstract</B></P> <P>Display Omitted</P> <P><B>Highlights</B></P> <P> <UL> <LI> Epigenetic and expression-based stemness indices measure oncogenic dedifferentiation </LI> <LI> Immune microenvironment content and PD-L1 levels associate with stemness indices </LI> <LI> Stemness index is increased in metastatic tumors and reveals intratumor heterogeneity </LI> <LI> Applying stemness indices reveals potential drug targets for anti-cancer therapies </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>