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However, current research often lacks a comprehensive perspective, focusing on specific mutation types and singular 3D structural levels. Here, pathological changes from chromosomes to nucleotides are systematically cataloged, including 10\u00a0789 interchromosomal translocations (ICTs), 18\u00a0863 structural variants (SVs), and 162\u00a0769 single nucleotide polymorphisms (SNPs). The multilayered analysis reveals that fewer than 10% of ICTs disrupt territories via potent 3D interactions, and only a minimal fraction of SVs disrupt compartments or intersect topologically associated domain structures, yet these events significantly influence gene expression. Pathogenic SNPs typically show reduced interactions within the 3D genomic space. To investigate the effects of variants in the context of 3D organization, a two\u2010phase scoring algorithm, 3DFunc, is developed to evaluate the pathogenicity of variant\u2013gene pairs in cancer. Using 3DFunc, IGHV3\u201023\u2032s critical role in chronic lymphocytic leukemia is identified and it is found that three pathological SNPs (rs6605578, rs7814783, rs2738144) interact with DEFA3. Additionally, 3DGAtlas is introduced, which provides a highly accessible 3D genome atlas and a valuable resource for exploring the pathological effects of genetic mutations in cancer.<\/jats:p>","DOI":"10.1002\/advs.202408420","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T03:17:39Z","timestamp":1743131859000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A 3D Genome Atlas of Genetic Variants and Their Pathological Effects in Cancer"],"prefix":"10.1002","volume":"12","author":[{"given":"Li","family":"Tang","sequence":"first","affiliation":[{"name":"School of Computer Science and Engineering Central South University  Changsha 410083 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew C.","family":"Hill","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center Massachusetts General Hospital  Boston MA 02129 USA"},{"name":"Cardiovascular Disease Initiative The Broad Institute of MIT and Harvard  Cambridge MA 02142 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingxing","family":"He","sequence":"additional","affiliation":[{"name":"School of Computer Science and Engineering Central South University  Changsha 410083 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhao","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Computer Science and Engineering Central South University  Changsha 410083 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zirui","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Computer Science and Engineering Central South University  Changsha 410083 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick T.","family":"Ellinor","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center Massachusetts General Hospital  Boston MA 02129 USA"},{"name":"Cardiovascular Disease Initiative The Broad Institute of MIT and Harvard  Cambridge MA 02142 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0188-1394","authenticated-orcid":false,"given":"Min","family":"Li","sequence":"additional","affiliation":[{"name":"School of Computer Science and Engineering Central South University  Changsha 410083 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,25]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04081-2"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.15302\/J-QB-022-0317"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/35066075"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1181369"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.12.014"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11279"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/19491034.2015.1106676"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.138"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0040138"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0768-0"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.11.021"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.04.004"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19800"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.179523"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature18962"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2008.11.011"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.175034.114"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073974"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep41071"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv009"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0480-5"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1235122"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16434-y"},{"key":"e_1_2_9_25_1","first-page":"D863","volume":"48","author":"Liu S.\u2010H.","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1018"},{"key":"e_1_2_9_27_1","volume":"47","author":"Tate J. 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