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To date, no comprehensive pan-cancer investigation of\n                    <jats:italic>DNA2<\/jats:italic>\n                    has been conducted. Employing TCGA cohorts and complementary public databases, we executed the first pan-cancer multi-omics study of\n                    <jats:italic>DNA2<\/jats:italic>\n                    , examining transcriptomic, genomic variations, survival, immune infiltration, single-cell functional states, protein\u2013protein interaction enrichment, and pharmacogenomic drug-response data across tumor profiles.\n                    <jats:italic>DNA2<\/jats:italic>\n                    was considerably overexpressed in 17 tumors compared with matching normal tissues. In endometrial cancer, the highest frequency of genetic changes (~\u20097%) was observed. Univariable analyses of survival showed that elevated\n                    <jats:italic>DNA2<\/jats:italic>\n                    expression was related to worse overall survival in malignancies, including adrenocortical carcinoma (HR\u2009=\u200917.06) and mesothelioma (HR\u2009=\u20092.67). Single-cell omics revealed a tumor-specific correlation between\n                    <jats:italic>DNA2<\/jats:italic>\n                    expression and functional annotations that encompass DNA damage, angiogenesis, and proliferation. Moreover,\n                    <jats:italic>DNA2<\/jats:italic>\n                    expression was consistently positively associated with regulatory T-cell subtypes, but negatively related with NK cells, and cytotoxic T cells in multiple tumors as per immune landscape profiling. According to the pharmacogenomic analysis from GDSC2 dataset, tumor cells that express higher\n                    <jats:italic>DNA2<\/jats:italic>\n                    are more sensitive to Tozasertib, and Daporinad. DNA2 is at the core of several interrelated modules, including flap processing, telomerase extension, and cell-cycle progression, according to the enrichment study. These findings have suggested\n                    <jats:italic>DNA2<\/jats:italic>\n                    as a therapeutic vulnerability in cancer, a context-dependent biomarker with implications for treatment response, prognosis, and immunity.\n                  <\/jats:p>","DOI":"10.1007\/s10142-026-01941-w","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:03:10Z","timestamp":1781668990000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multi-omics analysis positions DNA2 at the interface of genome integrity programs and tumor behavior in pan-cancer"],"prefix":"10.1007","volume":"26","author":[{"given":"Depanshi","family":"Pandit","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amardeep","family":"Dhillon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjiban","family":"Chakrabarty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3713-3646","authenticated-orcid":false,"given":"Ravindranath Sanganabasappa","family":"Bilachi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"1941_CR20","doi-asserted-by":"publisher","first-page":"2622","DOI":"10.3390\/ijms22052622","volume":"22","author":"\u00c1 Bartha","year":"2021","unstructured":"Bartha \u00c1, Gy\u0151rffy B (2021) TNMplot.com: a web tool for the comparison of gene expression in normal, tumor and metastatic tissues. 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