{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T19:20:04Z","timestamp":1754162404964,"version":"3.41.2"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Brain metastasis (BM) is one of the common ways of tumor metastasis and has a poor prognosis. This study aims to identify potential biomarkers from the perspective of somatic mutations, providing a basis for the prognosis evaluation and immunogenicity prediction of BM patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study collected the somatic mutation profiles and clinical information of a total of 421 patients with BM in Memorial Sloan Kettering Cancer Center (MSKCC). Non-negative matrix factorization was employed to extract the mutational process signatures operating in the genome. Consensus clustering analysis was utilized to identify mutation-related molecular subtypes. Through a comprehensive analysis of genomic mutations and copy number variations (CNV), biomarkers associated with outcomes and tumor immunogenicity were screened.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Non-small cell lung cancer, melanoma, and breast cancer were common primary tumors of BM, and these three tumor types exhibited better prognosis compared to other types. This study found that a higher tumor mutation burden (TMB) was significantly associated with a better prognosis of BM. A total of four mutational process signatures were extracted, and among them, a signature featured by C &amp;gt; T mutations and related to DNA damage repair was proven to be linked with an inferior outcome and a lower TMB. Through integrated genomic mutation analysis, <jats:italic>PTPRT<\/jats:italic> mutation was determined to associate with improved prognosis of BM. More importantly, patients carrying this mutation also harbored a better response to immunotherapy. CNV analysis indicated that <jats:italic>PTEN<\/jats:italic> deletion and <jats:italic>DUSP4<\/jats:italic> deletion were respectively associated with poorer and better outcomes in patients with BM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>By integrating the somatic mutation data of patients with BM, this study identified molecular biomarkers related to outcomes and immunogenicity from three perspectives: mutational process signatures, molecular subtypes, and genomic variations. Our findings provide clues for prognosis evaluation in BM patients. They also establish a theoretical basis for predicting immunotherapy efficacy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1607772","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T05:29:40Z","timestamp":1753853380000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A mutational process signature and genomic alterations associated with outcome and immunogenicity in cancers with brain 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