Cargando…

Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer

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 hypermethy...

Descripción completa

Detalles Bibliográficos
Autores principales: Hoadley, Katherine A., Yau, Christina, Hinoue, Toshinori, Wolf, Denise M., Lazar, Alexander J., Drill, Esther, Shen, Ronglai, Taylor, Alison M., Cherniack, Andrew D., Thorsson, Vésteinn, Akbani, Rehan, Bowlby, Reanne, Wong, Christopher K., Wiznerowicz, Maciej, Sanchez-Vega, Francisco, Robertson, A. Gordon, Schneider, Barbara G., Lawrence, Michael S., Noushmehr, Houtan, Malta, Tathiane M., Stuart, Joshua M., Benz, Christopher C., Laird, Peter W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5957518/
https://www.ncbi.nlm.nih.gov/pubmed/29625048
http://dx.doi.org/10.1016/j.cell.2018.03.022
_version_ 1783324075759763456
author Hoadley, Katherine A.
Yau, Christina
Hinoue, Toshinori
Wolf, Denise M.
Lazar, Alexander J.
Drill, Esther
Shen, Ronglai
Taylor, Alison M.
Cherniack, Andrew D.
Thorsson, Vésteinn
Akbani, Rehan
Bowlby, Reanne
Wong, Christopher K.
Wiznerowicz, Maciej
Sanchez-Vega, Francisco
Robertson, A. Gordon
Schneider, Barbara G.
Lawrence, Michael S.
Noushmehr, Houtan
Malta, Tathiane M.
Stuart, Joshua M.
Benz, Christopher C.
Laird, Peter W.
author_facet Hoadley, Katherine A.
Yau, Christina
Hinoue, Toshinori
Wolf, Denise M.
Lazar, Alexander J.
Drill, Esther
Shen, Ronglai
Taylor, Alison M.
Cherniack, Andrew D.
Thorsson, Vésteinn
Akbani, Rehan
Bowlby, Reanne
Wong, Christopher K.
Wiznerowicz, Maciej
Sanchez-Vega, Francisco
Robertson, A. Gordon
Schneider, Barbara G.
Lawrence, Michael S.
Noushmehr, Houtan
Malta, Tathiane M.
Stuart, Joshua M.
Benz, Christopher C.
Laird, Peter W.
author_sort Hoadley, Katherine A.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5957518
institution National Center for Biotechnology Information
language English
publishDate 2018
record_format MEDLINE/PubMed
spelling pubmed-59575182019-04-05 Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer Hoadley, Katherine A. Yau, Christina Hinoue, Toshinori Wolf, Denise M. Lazar, Alexander J. Drill, Esther Shen, Ronglai Taylor, Alison M. Cherniack, Andrew D. Thorsson, Vésteinn Akbani, Rehan Bowlby, Reanne Wong, Christopher K. Wiznerowicz, Maciej Sanchez-Vega, Francisco Robertson, A. Gordon Schneider, Barbara G. Lawrence, Michael S. Noushmehr, Houtan Malta, Tathiane M. Stuart, Joshua M. Benz, Christopher C. Laird, Peter W. Cell Article 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. 2018-04-05 /pmc/articles/PMC5957518/ /pubmed/29625048 http://dx.doi.org/10.1016/j.cell.2018.03.022 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Hoadley, Katherine A.
Yau, Christina
Hinoue, Toshinori
Wolf, Denise M.
Lazar, Alexander J.
Drill, Esther
Shen, Ronglai
Taylor, Alison M.
Cherniack, Andrew D.
Thorsson, Vésteinn
Akbani, Rehan
Bowlby, Reanne
Wong, Christopher K.
Wiznerowicz, Maciej
Sanchez-Vega, Francisco
Robertson, A. Gordon
Schneider, Barbara G.
Lawrence, Michael S.
Noushmehr, Houtan
Malta, Tathiane M.
Stuart, Joshua M.
Benz, Christopher C.
Laird, Peter W.
Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer
title Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer
title_full Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer
title_fullStr Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer
title_full_unstemmed Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer
title_short Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer
title_sort cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5957518/
https://www.ncbi.nlm.nih.gov/pubmed/29625048
http://dx.doi.org/10.1016/j.cell.2018.03.022
work_keys_str_mv AT hoadleykatherinea celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT yauchristina celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT hinouetoshinori celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT wolfdenisem celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT lazaralexanderj celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT drillesther celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT shenronglai celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT tayloralisonm celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT cherniackandrewd celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT thorssonvesteinn celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT akbanirehan celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT bowlbyreanne celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT wongchristopherk celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT wiznerowiczmaciej celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT sanchezvegafrancisco celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT robertsonagordon celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT schneiderbarbarag celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT lawrencemichaels celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT noushmehrhoutan celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT maltatathianem celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT stuartjoshuam celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT benzchristopherc celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer
AT lairdpeterw celloforiginpatternsdominatethemolecularclassificationof10000tumorsfrom33typesofcancer