Comprehensive Genomic Dependency Landscape of Human Colon Cancer

Comprehensive Genomic Dependency Landscape of Human Colon Cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Biological Sciences - Article Comprehensive Genomic Dependency Landscape of Human Colon Cancer Sana Khalili, Atefeh Mohseninia, Changlong Liu, Carolyn E. Banister, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4438536/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 14 Mar, 2025 Read the published version in Communications Biology → Version 1 posted You are reading this latest preprint version Abstract Identifying genetic dependencies in human colon cancer could help identify effective treatment strategies. Genome-wide CRISPR-Cas9 dropout screens have the potential to reveal genetic dependencies, some of which could be exploited as therapeutic targets using existing drugs. In this study, we comprehensively characterized genetic dependencies present in a colon cancer organoid avatar, and validated tumor-specific selectivity of select pharmacologic agents. We conducted a genome-wide CRISPR dropout screen to elucidate the genetic dependencies that interacted with select driver somatic mutations. We found distinct genetic dependencies that interacted with WNT, MAPK, PI3K, TP53, and mismatch repair pathways and validated targets that could be exploited as treatments for this specific subtype of colon cancer. These findings demonstrate the utility of functional genomic screening in the context of personalized medicine. Biological sciences/Cancer/Cancer genomics Biological sciences/Cancer/Gastrointestinal cancer/Colorectal cancer/Colon cancer Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplemnetaryTable1.xlsx Supplementary Table 1 SupplementaryTable2.xlsx Supplementary Table 2 SupplementaryTable3.xlsx Supplementary Table 3 SupplementaryTable4.xlsx Supplementary Table 4 Cite Share Download PDF Status: Published Journal Publication published 14 Mar, 2025 Read the published version in Communications Biology → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4438536","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":310055522,"identity":"11a15994-876d-4ce7-9015-846a727fbd17","order_by":0,"name":"Sana Khalili","email":"","orcid":"","institution":"University of South Carolina, Columbia SC","correspondingAuthor":false,"prefix":"","firstName":"Sana","middleName":"","lastName":"Khalili","suffix":""},{"id":310055523,"identity":"62319f05-a451-420d-a348-40ffb7c8df3e","order_by":1,"name":"Atefeh Mohseninia","email":"","orcid":"","institution":"University of South Carolina, Columbia SC","correspondingAuthor":false,"prefix":"","firstName":"Atefeh","middleName":"","lastName":"Mohseninia","suffix":""},{"id":310055524,"identity":"4c82fccc-c5c4-474d-97ea-9a98bd310d5a","order_by":2,"name":"Changlong Liu","email":"","orcid":"","institution":"University of South Carolina, Columbia SC","correspondingAuthor":false,"prefix":"","firstName":"Changlong","middleName":"","lastName":"Liu","suffix":""},{"id":310055525,"identity":"d5752fa9-44c5-487b-8a22-95e0e0511419","order_by":3,"name":"Carolyn E. 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