{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:38:28Z","timestamp":1791315508928,"version":"4.3.1"},"reference-count":45,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T00:00:00Z","timestamp":1709164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007076","name":"Associazione Italiana per la Ricerca sul Cancro (AIRC)","doi-asserted-by":"publisher","award":["27367"],"award-info":[{"award-number":["27367"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>RAS mutations involving codon 61 are rare in metastatic colorectal cancer (mCRC), accounting for only 1\u20134%, but they have recently been identified with high frequency in the circulating tumor DNA (ctDNA) of patients with secondary resistance to anti-EGFRs. This retrospective monocentric study aimed to investigate the clinical phenotype and prognostic performance of codon 61 RAS-mutated mCRC. Fifty patients with codon 61 RAS-mutated mCRC treated at our institution between January 2013 and December 2021 were enrolled. Additional datasets of codon 61 RAS wild-type mCRCs (648 patients) were used as comparators. The endpoint for prognostic assessment was overall survival (OS). Metastatic involvement of the peritoneum or ovary was significantly more frequent in codon 61 RAS-mutated mCRC compared to codon 61 RAS wild-type (54 vs. 28.5%), non-codon 61 RAS-mutated (35.6%), BRAF V600E-mutated (25%), and RAS\/BRAF wild-type (20.5%) cohorts. At a median follow up of 96.2 months, the median OS for codon 61 RAS-mutated patients was significantly shorter compared to RAS\/BRAF wild-type (26.9 vs. 36.0 months, HR 0.56) patients, while no significant difference was observed compared to non-codon 61 RAS-mutated and BRAF V600E-mutated patients. We showed a negative prognostic impact and a statistically significant correlation between codon 61 RAS mutations and metastatic involvement of the peritoneum and ovary.<\/jats:p>","DOI":"10.3390\/cancers16050988","type":"journal-article","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T08:13:44Z","timestamp":1709194424000},"page":"988","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Focus on RAS Codon 61 Mutations in Metastatic Colorectal Cancer: A Retrospective Analysis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9669-8602","authenticated-orcid":false,"given":"Francesco","family":"Schietroma","sequence":"first","affiliation":[{"name":"Medical Oncology, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annunziato","family":"Anghelone","sequence":"additional","affiliation":[{"name":"Medical Oncology, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giustina","family":"Valente","sequence":"additional","affiliation":[{"name":"Medical Oncology, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viria","family":"Beccia","sequence":"additional","affiliation":[{"name":"Medical Oncology, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Caira","sequence":"additional","affiliation":[{"name":"Medical Oncology, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexia","family":"Spring","sequence":"additional","affiliation":[{"name":"Medical Oncology, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Trovato","sequence":"additional","affiliation":[{"name":"Medical Oncology, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"Di Bello","sequence":"additional","affiliation":[{"name":"Medical Oncology, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Ceccarelli","sequence":"additional","affiliation":[{"name":"Medical Oncology, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Chiofalo","sequence":"additional","affiliation":[{"name":"Medical Oncology, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Perazzo","sequence":"additional","affiliation":[{"name":"Medical Oncology, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Bensi","sequence":"additional","affiliation":[{"name":"Medical Oncology, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0833-4334","authenticated-orcid":false,"given":"Angelo","family":"Minucci","sequence":"additional","affiliation":[{"name":"Departmental Unit of Molecular and Genomic Diagnostics, Genomics Core Facility, Gemelli Science and Technology Park (G-STeP), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Urbani","sequence":"additional","affiliation":[{"name":"Clinical Chemistry, Biochemistry and Molecular Biology Operations, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1739-4758","authenticated-orcid":false,"given":"Luigi Maria","family":"Larocca","sequence":"additional","affiliation":[{"name":"Patologia Oncoematologica, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanit\u00e0 Pubblica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Basso","sequence":"additional","affiliation":[{"name":"Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4004-9098","authenticated-orcid":false,"given":"Carmelo","family":"Pozzo","sequence":"additional","affiliation":[{"name":"Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3864-0719","authenticated-orcid":false,"given":"Lisa","family":"Salvatore","sequence":"additional","affiliation":[{"name":"Medical Oncology, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"},{"name":"Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Alessandra","family":"Calegari","sequence":"additional","affiliation":[{"name":"Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giampaolo","family":"Tortora","sequence":"additional","affiliation":[{"name":"Medical Oncology, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"},{"name":"Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1038\/nm.3967","article-title":"The consensus molecular subtypes of colorectal cancer","volume":"21","author":"Guinney","year":"2015","journal-title":"Nat. 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