| Full text | |
| Author(s): Show less - |
Malta, Tathiane M.
[1, 2]
;
Sokolov, Artem
[3]
;
Gentles, Andrew J.
[4]
;
Burzykowski, Tomasz
[5]
;
Poisson, Laila
[2]
;
Weinstein, John N.
[6]
;
Kaminska, Bozena
[7]
;
Huelsken, Joerg
[8]
;
Omberg, Larsson
[9]
;
Gevaert, Olivier
[4]
;
Colaprico, Antonio
[10, 11]
;
Czerwinska, Patrycja
[12]
;
Mazurek, Sylwia
[12, 13]
;
Mishra, Lopa
[14]
;
Heyn, Holger
[15]
;
Krasnitz, Alex
[16]
;
Godwin, Andrew K.
[17]
;
Lazar, Alexander J.
[6]
;
Stuart, Joshua M.
[18]
;
Hoadley, Katherine A.
[19]
;
Laird, Peter W.
[20]
;
Noushmehr, Houtan
[1, 2]
;
Wiznerowicz, Maciej
[2, 12, 21, 22]
;
Network, Cancer Genome Atlas Res
Total Authors: 24
|
| Affiliation: Show less - | [1] Univ Sao Paulo, BR-14049 Ribeirao Preto, SP - Brazil
[2] Henry Ford Hlth Syst, Detroit, MI 48202 - USA
[3] Harvard Med Sch, Boston, MA 02115 - USA
[4] Stanford Univ, Palo Alto, CA 94305 - USA
[5] Hasselt Univ, B-3590 Diepenbeek - Belgium
[6] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 - USA
[7] PAS, Nencki Inst Expt Biol, PL-02093 Warsaw - Poland
[8] Swiss Fed Inst Technol Lausanne, EPFL, CH-1015 Lausanne - Switzerland
[9] Sage Bionetworks, Seattle, WA 98109 - USA
[10] Univ Libre Bruxelles, B-1050 Brussels - Belgium
[11] Interuniv Inst Bioinformat Brussels IB2, B-1050 Brussels - Belgium
[12] Poznan Univ Med Sci, PL-61701 Poznan - Poland
[13] Med Univ Warsaw, Postgrad Sch Mol Med, PL-02109 Warsaw - Poland
[14] George Washington Univ, Washington, DC - USA
[15] Ctr Genom Regulat CNAG CRG, Barcelona 08003 - Spain
[16] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 - USA
[17] Univ Kansas, Med Ctr, Kansas City, KS 66160 - USA
[18] Univ Calif Santa Cruz, Santa Cruz, CA 95064 - USA
[19] Univ N Carolina, Chapel Hill, NC 27599 - USA
[20] Van Andel Res Inst, Grand Rapids, MI 49503 - USA
[21] Greater Poland Canc Ctr, PL-61866 Poznan - Poland
[22] Int Inst Mol Oncol, PL-60203 Poznan - Poland
Total Affiliations: 22
|
| Document type: | Journal article |
| Source: | Cell; v. 173, n. 2, p. 338+, APR 5 2018. |
| Web of Science Citations: | 92 |
| Abstract | |
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. (AU) | |
| FAPESP's process: | 16/06488-3 - Integrative epigenomic analysis of high and low Glioma-CpG island Methylator Phenotype (G-CIMP): characterization and methods development |
| Grantee: | Thaís Sarraf Sabedot |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 14/08321-3 - Identification and characterization of functional genomic elements associated with progression of low to high grade glioma: integrative study of genome and epigenome |
| Grantee: | Camila Ferreira de Souza |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 15/07925-5 - Open source software statistical tools to aid in analyzing and integrating large cancer epigenomic datasets in order to decipher and understand regulatory networks |
| Grantee: | Houtan Noushmehr |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 16/01975-3 - Defining stem cell epigenomic signatures in 33 different tumor types across 9000+ tumor samples |
| Grantee: | Tathiane Maistro Malta Pereira |
| Support Opportunities: | Scholarships abroad - Research Internship - Post-doctor |
| FAPESP's process: | 16/01389-7 - Bioinformatic tool to integrate and understand aberrant epigenomic and genomic changes associated with cancer: methods, development and analysis |
| Grantee: | Tiago Chedraoui Silva |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 16/15485-8 - Clinical biomarkers in central nervous system tumors |
| Grantee: | Camila Ferreira de Souza |
| Support Opportunities: | Scholarships abroad - Research Internship - Post-doctor |
| FAPESP's process: | 14/02245-3 - Identification of epigenomic signatures that define open chromatin regulatory networks associated with mesenchymal differentiation from human pluripotent stem cells |
| Grantee: | Tathiane Maistro Malta Pereira |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 16/10436-9 - Development and enhancement of bioinformatic tools to integrate and understand aberrant epigenomic and genomic changes associated with cancer: methods, development and analysis |
| Grantee: | Tiago Chedraoui Silva |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate (Direct) |
| FAPESP's process: | 16/12329-5 - Chromatin accessibility and DNA methylation changes associated with high and low Glioma-CpG island methylator phenotype (G-CIMP) |
| Grantee: | Thaís Sarraf Sabedot |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate (Direct) |