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Single-cell chromatin accessibility reveals malignant regulatory programs in primary human cancers.
Sundaram, Laksshman; Kumar, Arvind; Zatzman, Matthew; Salcedo, Adriana; Ravindra, Neal; Shams, Shadi; Louie, Bryan H; Bagdatli, S Tansu; Myers, Matthew A; Sarmashghi, Shahab; Choi, Hyo Young; Choi, Won-Young; Yost, Kathryn E; Zhao, Yanding; Granja, Jeffrey M; Hinoue, Toshinori; Hayes, D Neil; Cherniack, Andrew; Felau, Ina; Choudhry, Hani; Zenklusen, Jean C; Farh, Kyle Kai-How; McPherson, Andrew; Curtis, Christina; Laird, Peter W; Demchok, John A; Yang, Liming; Tarnuzzer, Roy; Caesar-Johnson, Samantha J; Wang, Zhining; Doane, Ashley S; Khurana, Ekta; Castro, Mauro A A; Lazar, Alexander J; Broom, Bradley M; Weinstein, John N; Akbani, Rehan; Kumar, Shwetha V; Raphael, Benjamin J; Wong, Christopher K; Stuart, Joshua M; Safavi, Rojin; Benz, Christopher C; Johnson, Benjamin K; Kyi, Cindy; Shen, Hui; Corces, M Ryan; Chang, Howard Y; Greenleaf, William J.
Afiliação
  • Sundaram L; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Kumar A; Department of Computer Science, Stanford University, Stanford, CA, USA.
  • Zatzman M; Illumina AI laboratory, Illumina Inc, Foster City, CA, USA.
  • Salcedo A; NVIDIA Bio Research, NVIDIA, Santa Clara, CA, USA.
  • Ravindra N; Illumina AI laboratory, Illumina Inc, Foster City, CA, USA.
  • Shams S; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Louie BH; Illumina AI laboratory, Illumina Inc, Foster City, CA, USA.
  • Bagdatli ST; Illumina AI laboratory, Illumina Inc, Foster City, CA, USA.
  • Myers MA; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Sarmashghi S; Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA.
  • Choi HY; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
  • Choi WY; Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA.
  • Yost KE; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
  • Zhao Y; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Granja JM; Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA.
  • Hinoue T; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
  • Hayes DN; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Cherniack A; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Felau I; Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
  • Choudhry H; Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
  • Zenklusen JC; UTHSC Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA.
  • Farh KK; Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA.
  • McPherson A; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
  • Curtis C; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Laird PW; Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA.
  • Demchok JA; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Yang L; Center for Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA.
  • Tarnuzzer R; Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
  • Caesar-Johnson SJ; Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
  • Wang Z; UTHSC Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA.
  • Doane AS; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Khurana E; National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Castro MAA; Department of Biochemistry, Faculty of Science, Cancer and Mutagenesis Unit, King Fahd Center for Medical Research, King Abdulaziz University, Jeddah, Saudi Arabia.
  • Lazar AJ; National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Broom BM; Illumina AI laboratory, Illumina Inc, Foster City, CA, USA.
  • Weinstein JN; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Akbani R; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Kumar SV; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
  • Raphael BJ; Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Wong CK; Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.
  • Stuart JM; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Safavi R; Center for Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA.
  • Johnson BK; Center for Cancer Genomics, National Cancer Institute, Bethesda, MD 20892, USA.
  • Kyi C; Center for Cancer Genomics, National Cancer Institute, Bethesda, MD 20892, USA.
  • Shen H; Center for Cancer Genomics, National Cancer Institute, Bethesda, MD 20892, USA.
  • Corces MR; Center for Cancer Genomics, National Cancer Institute, Bethesda, MD 20892, USA.
  • Chang HY; Center for Biomedical Informatics and Information Technology, National Cancer Institute, NIH, 9609 Medical Center Drive, Rockville, MD 20850, USA.
  • Greenleaf WJ; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10065, USA.
Science ; 385(6713): eadk9217, 2024 09 06.
Article em En | MEDLINE | ID: mdl-39236169
ABSTRACT
To identify cancer-associated gene regulatory changes, we generated single-cell chromatin accessibility landscapes across eight tumor types as part of The Cancer Genome Atlas. Tumor chromatin accessibility is strongly influenced by copy number alterations that can be used to identify subclones, yet underlying cis-regulatory landscapes retain cancer type-specific features. Using organ-matched healthy tissues, we identified the "nearest healthy" cell types in diverse cancers, demonstrating that the chromatin signature of basal-like-subtype breast cancer is most similar to secretory-type luminal epithelial cells. Neural network models trained to learn regulatory programs in cancer revealed enrichment of model-prioritized somatic noncoding mutations near cancer-associated genes, suggesting that dispersed, nonrecurrent, noncoding mutations in cancer are functional. Overall, these data and interpretable gene regulatory models for cancer and healthy tissue provide a framework for understanding cancer-specific gene regulation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cromatina / Regulação Neoplásica da Expressão Gênica / Análise de Célula Única / Neoplasias Limite: Humans Idioma: En Revista: Science Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cromatina / Regulação Neoplásica da Expressão Gênica / Análise de Célula Única / Neoplasias Limite: Humans Idioma: En Revista: Science Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos