{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:13:42Z","timestamp":1789676022780,"version":"4.0.1"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":137,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004829","name":"Department of Science and Technology of Sichuan Province","doi-asserted-by":"publisher","award":["2023ZHYZ0009"],"award-info":[{"award-number":["2023ZHYZ0009"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Neurofibromin 1 (NF1) is a tumor suppressor gene frequently altered across diverse cancer types, yet its biological significance in ovarian cancer remains incompletely characterized. Here, we integrated cohort\u2010scale somatic mutation profiling with functional validation to characterize the mutational and cellular consequences of NF1 loss in ovarian cancer. Somatic mutation data from the TCGA ovarian cancer cohort were analyzed to define NF1\u2010associated mutation types, tumor mutational burden, mutational signatures, and co\u2010occurring alterations in DNA damage repair (DDR) pathways, together with pathway\u2010 and gene set\u2013level functional enrichment analyses. NF1 alterations were predominantly truncating and consistent with loss\u2010of\u2010function events. NF1\u2010mutant tumors did not exhibit increased global tumor mutational burden or uniform APOBEC hypermutation but showed distinct single\u2010nucleotide substitution patterns and frequent comutations in core DDR\u2010related genes. Functional enrichment analyses further highlighted coordinated involvement of pathways related to DNA replication, RNA processing, and proteostasis. Clinically, NF1 mutation was not independently associated with overall survival. Stable NF1 knockdown ovarian cancer models showed that NF1 depletion did not affect basal proliferation but increased sensitivity to hydroxyurea\u2010induced replication stress, accompanied by increased\n                    <jats:italic>\u03b3<\/jats:italic>\n                    H2AX accumulation. Together, these findings indicate that NF1 loss defines a DNA damage\u2013associated mutational and cellular state in ovarian cancer. Rather than acting as a direct prognostic determinant, NF1 mutation appears to increase vulnerability to replication stress and DNA damage, providing functional insight into its role in ovarian tumor biology.\n                  <\/jats:p>","DOI":"10.1155\/humu\/9333284","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T08:56:31Z","timestamp":1779094591000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrative Genomic and Functional Analysis Reveals NF1 Loss as a Modifier of DNA Damage and Replication Stress Responses in Ovarian 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