@article{5b39dcc86fc840609e49e3c2e4c3b062,
title = "Single-cell chromatin accessibility reveals malignant regulatory programs in primary human cancers",
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.",
author = "{Cancer Genome Atlas Analysis Network‡} and Laksshman Sundaram and Arvind Kumar and Matthew Zatzman and Adriana Salcedo and Neal Ravindra and Shadi Shams and Louie, {Brian H.} and Bagdatli, {S. Tansu} and Myers, {Matthew A.} and Shahab Sarmashghi and Choi, {Hyo Young} and Choi, {Won Young} and Yost, {Kathryn E.} and Yanding Zhao and Granja, {Jeffrey M.} and Toshinori Hinoue and Hayes, {D. Neil} and Andrew Cherniack and Ina Felau and Hani Choudhry and Zenklusen, {Jean C.} and Farh, {Kyle Kai How} and Andrew McPherson and Christina Curtis and Laird, {Peter W.} and Corces, {M. Ryan} and Chang, {Howard Y.} and Greenleaf, {William J.} and Demchok, {John A.} and Liming Yang and Roy Tarnuzzer and Caesar-Johnson, {Samantha J.} and Zhining Wang and Doane, {Ashley S.} and Ekta Khurana and Castro, {Mauro A.A.} and Lazar, {Alexander J.} and Broom, {Bradley M.} and Weinstein, {John N.} and Rehan Akbani and Kumar, {Shwetha V.} and Raphael, {Benjamin J.} and Wong, {Christopher K.} and Stuart, {Joshua M.} and Rojin Safavi and Benz, {Christopher C.} and Johnson, {Benjamin K.} and Cindy Kyi and Hui Shen",
year = "2024",
month = sep,
day = "6",
doi = "10.1126/science.adk9217",
language = "American English",
volume = "385",
pages = "eadk9217",
journal = "Science (New York, N.Y.)",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6713",
}