TY - JOUR
T1 - Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer
AU - The Cancer Genome Atlas Network
AU - Hoadley, Katherine A.
AU - Yau, Christina
AU - Hinoue, Toshinori
AU - Wolf, Denise M.
AU - Lazar, Alexander J.
AU - Drill, Esther
AU - Shen, Ronglai
AU - Taylor, Alison M.
AU - Cherniack, Andrew D.
AU - Thorsson, Vésteinn
AU - Akbani, Rehan
AU - Bowlby, Reanne
AU - Wong, Christopher K.
AU - Wiznerowicz, Maciej
AU - Sanchez-Vega, Francisco
AU - Robertson, A. Gordon
AU - Schneider, Barbara G.
AU - Lawrence, Michael S.
AU - Noushmehr, Houtan
AU - Malta, Tathiane M.
AU - Caesar-Johnson, Samantha J.
AU - Demchok, John A.
AU - Felau, Ina
AU - Kasapi, Melpomeni
AU - Ferguson, Martin L.
AU - Hutter, Carolyn M.
AU - Sofia, Heidi J.
AU - Tarnuzzer, Roy
AU - Wang, Zhining
AU - Yang, Liming
AU - Zenklusen, Jean C.
AU - Zhang, Jiashan (Julia)
AU - Chudamani, Sudha
AU - Liu, Jia
AU - Lolla, Laxmi
AU - Naresh, Rashi
AU - Pihl, Todd
AU - Sun, Qiang
AU - Wan, Yunhu
AU - Wu, Ye
AU - Cho, Juok
AU - Wilkerson, Matthew D.
AU - Deyarmin, Brenda
AU - Hu, Hai
AU - Kvecher, Leonid
AU - Somiari, Stella
AU - Fantacone-Campbell, J. Leigh
AU - Hooke, Jeffrey A.
AU - Kovatich, Albert J.
AU - Shriver, Craig D.
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/4/5
Y1 - 2018/4/5
N2 - We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. We performed molecular clustering using data on chromosome-arm-level aneuploidy, DNA hypermethylation, mRNA, and miRNA expression levels and reverse-phase protein arrays, of which all, except for aneuploidy, revealed clustering primarily organized by histology, tissue type, or anatomic origin. The influence of cell type was evident in DNA-methylation-based clustering, even after excluding sites with known preexisting tissue-type-specific methylation. Integrative clustering further emphasized the dominant role of cell-of-origin patterns. Molecular similarities among histologically or anatomically related cancer types provide a basis for focused pan-cancer analyses, such as pan-gastrointestinal, pan-gynecological, pan-kidney, and pan-squamous cancers, and those related by stemness features, which in turn may inform strategies for future therapeutic development. Comprehensive, integrated molecular analysis identifies molecular relationships across a large diverse set of human cancers, suggesting future directions for exploring clinical actionability in cancer treatment.
AB - We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. We performed molecular clustering using data on chromosome-arm-level aneuploidy, DNA hypermethylation, mRNA, and miRNA expression levels and reverse-phase protein arrays, of which all, except for aneuploidy, revealed clustering primarily organized by histology, tissue type, or anatomic origin. The influence of cell type was evident in DNA-methylation-based clustering, even after excluding sites with known preexisting tissue-type-specific methylation. Integrative clustering further emphasized the dominant role of cell-of-origin patterns. Molecular similarities among histologically or anatomically related cancer types provide a basis for focused pan-cancer analyses, such as pan-gastrointestinal, pan-gynecological, pan-kidney, and pan-squamous cancers, and those related by stemness features, which in turn may inform strategies for future therapeutic development. Comprehensive, integrated molecular analysis identifies molecular relationships across a large diverse set of human cancers, suggesting future directions for exploring clinical actionability in cancer treatment.
KW - TCGA
KW - cancer
KW - cell-of-origin
KW - genome
KW - methylome
KW - organs
KW - proteome
KW - subtypes
KW - tissues
KW - transcriptome
UR - http://www.scopus.com/inward/record.url?scp=85044737247&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2018.03.022
DO - 10.1016/j.cell.2018.03.022
M3 - Article
C2 - 29625048
AN - SCOPUS:85044737247
SN - 0092-8674
VL - 173
SP - 291-304.e6
JO - Cell
JF - Cell
IS - 2
ER -