{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T01:03:02Z","timestamp":1779670982629,"version":"3.53.1"},"reference-count":51,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sardinian Regional Government"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Colorectal cancer (CRC) is the third most diagnosed malignancy and the second leading cause of cancer-related mortality worldwide. Recent therapeutic advancements have significantly improved clinical management, underscoring the importance of routine molecular profiling to guide personalised treatment strategies. This study aims to evaluate the prognostic impact of main molecular alterations\u2014including allele frequency (AF) of RAS mutations\u2014on survival outcomes in a real-world hospital-based cohort of patients with metastatic CRC. Methods: A total of 208 consecutive patients with a histologically confirmed diagnosis of CRC and complete clinical, molecular, and survival data were retrospectively analysed. Somatic mutations in KRAS, NRAS, BRAF, and the occurrence of microsatellite instability (MSI) were assessed using pyrosequencing and real-time PCR assays, respectively, on formalin-fixed, paraffin-embedded tumour samples. Associations between mutational status, clinicopathological parameters, and overall survival (OS) were evaluated. Results: Overall, 138 patients (66.3%) harboured at least one somatic mutation: 115 (55.3%) in KRAS, 8 (3.8%) in NRAS, and 15 (7.2%) in BRAF. MSI was detected in 17\/208 (8.2%) patients. A statistically significant improvement in OS was observed in patients lacking mutations in any of the three genes\u2014referred to as wild-type (WT) patients\u2014with BRAF mutated cases showing the worst survival (p = 0.041). Increasing age at the time of first-line therapy for advanced disease stage was associated with a statistically significant increase in the hazard of death (p = 0.031). Conclusions: In the advanced disease stage, RAS\/BRAF wild-type colorectal cancers were significantly associated with a survival advantage.<\/jats:p>","DOI":"10.3390\/cancers18111708","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:30:33Z","timestamp":1779669033000},"page":"1708","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Driver Genetic Alterations on Survival in Metastatic Colorectal Cancer Patients from a Genetically Homogeneous Sardinian Population: A Real-World Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2945-0657","authenticated-orcid":false,"given":"Grazia","family":"Palomba","sequence":"first","affiliation":[{"name":"Unit of Cancer Genetics, Institute of Genetic Biomedical Research (IRGB), National Research Council (CNR), Traversa La Crucca 3, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6371-1112","authenticated-orcid":false,"given":"Luca","family":"Nuvoli","sequence":"additional","affiliation":[{"name":"Unit of Cancer Genetics, Institute of Genetic Biomedical Research (IRGB), National Research Council (CNR), Traversa La Crucca 3, 07100 Sassari, Italy"},{"name":"University Hospital (AOU) of Sassari, Viale San Pietro 43, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Sini","sequence":"additional","affiliation":[{"name":"Unit of Cancer Genetics, Institute of Genetic Biomedical Research (IRGB), National Research Council (CNR), Traversa La Crucca 3, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni Battista","family":"Maestrale","sequence":"additional","affiliation":[{"name":"Unit of Cancer Genetics, Institute of Genetic Biomedical Research (IRGB), National Research Council (CNR), Traversa La Crucca 3, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Doro","sequence":"additional","affiliation":[{"name":"Unit of Cancer Genetics, Institute of Genetic Biomedical Research (IRGB), National Research Council (CNR), Traversa La Crucca 3, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9844-1052","authenticated-orcid":false,"given":"Laura","family":"Frogheri","sequence":"additional","affiliation":[{"name":"Unit of Cancer Genetics, Institute of Genetic Biomedical Research (IRGB), National Research Council (CNR), Traversa La Crucca 3, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Persico","sequence":"additional","affiliation":[{"name":"Unit of Cancer Genetics, Institute of Genetic Biomedical Research (IRGB), National Research Council (CNR), Traversa La Crucca 3, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8396-0968","authenticated-orcid":false,"given":"Angelo","family":"Zinellu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide Adriano","family":"Santeufemia","sequence":"additional","affiliation":[{"name":"Oncology Unit, Civil Hospital, Via Don Minzoni, 07041 Alghero, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5485-6056","authenticated-orcid":false,"given":"Panagiotis","family":"Paliogiannis","sequence":"additional","affiliation":[{"name":"University Hospital (AOU) of Sassari, Viale San Pietro 43, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7538-1229","authenticated-orcid":false,"given":"Daniele","family":"Delogu","sequence":"additional","affiliation":[{"name":"University Hospital (AOU) of Sassari, Viale San Pietro 43, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2395-4475","authenticated-orcid":false,"given":"Fabrizio","family":"Scognamillo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Pharmacy, University of Sassari, Viale San Pietro 43, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4350-2276","authenticated-orcid":false,"given":"Giuseppe","family":"Palmieri","sequence":"additional","affiliation":[{"name":"Unit of Cancer Genetics, Institute of Genetic Biomedical Research (IRGB), National Research Council (CNR), Traversa La Crucca 3, 07100 Sassari, Italy"},{"name":"Immuno-Oncology & Targeted Cancer Biotherapies, University of Sassari, Viale San Pietro 43, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,23]]},"reference":[{"key":"ref_1","unstructured":"(2026, March 08). 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