Focus on <i>RAS</i> Codon 61 Mutations in Metastatic Colorectal Cancer: A Retrospective Analysis
<i>RAS</i> mutations involving codon 61 are rare in metastatic colorectal cancer (mCRC), accounting for only 1–4%, 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 monoc...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/5/988 |
| _version_ | 1797264727044259840 |
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| author | Francesco Schietroma Annunziato Anghelone Giustina Valente Viria Beccia Giulia Caira Alexia Spring Giovanni Trovato Armando Di Bello Anna Ceccarelli Laura Chiofalo Serena Perazzo Maria Bensi Angelo Minucci Andrea Urbani Luigi Maria Larocca Michele Basso Carmelo Pozzo Lisa Salvatore Maria Alessandra Calegari Giampaolo Tortora |
| author_facet | Francesco Schietroma Annunziato Anghelone Giustina Valente Viria Beccia Giulia Caira Alexia Spring Giovanni Trovato Armando Di Bello Anna Ceccarelli Laura Chiofalo Serena Perazzo Maria Bensi Angelo Minucci Andrea Urbani Luigi Maria Larocca Michele Basso Carmelo Pozzo Lisa Salvatore Maria Alessandra Calegari Giampaolo Tortora |
| author_sort | Francesco Schietroma |
| collection | DOAJ |
| description | <i>RAS</i> mutations involving codon 61 are rare in metastatic colorectal cancer (mCRC), accounting for only 1–4%, 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 <i>RAS</i>-mutated mCRC. Fifty patients with codon 61 <i>RAS</i>-mutated mCRC treated at our institution between January 2013 and December 2021 were enrolled. Additional datasets of codon 61 <i>RAS</i> 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 <i>RAS</i>-mutated mCRC compared to codon 61 <i>RAS</i> wild-type (54 vs. 28.5%), non-codon 61 <i>RAS</i>-mutated (35.6%), <i>BRAF</i> V600E-mutated (25%), and <i>RAS</i>/<i>BRAF</i> wild-type (20.5%) cohorts. At a median follow up of 96.2 months, the median OS for codon 61 <i>RAS</i>-mutated patients was significantly shorter compared to <i>RAS</i>/<i>BRAF</i> wild-type (26.9 vs. 36.0 months, HR 0.56) patients, while no significant difference was observed compared to non-codon 61 <i>RAS</i>-mutated and <i>BRAF</i> V600E-mutated patients. We showed a negative prognostic impact and a statistically significant correlation between codon 61 <i>RAS</i> mutations and metastatic involvement of the peritoneum and ovary. |
| first_indexed | 2024-04-25T00:33:29Z |
| format | Article |
| id | doaj.art-87734da2fc384253adfb11fae850cecc |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-04-25T00:33:29Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-87734da2fc384253adfb11fae850cecc2024-03-12T16:41:06ZengMDPI AGCancers2072-66942024-02-0116598810.3390/cancers16050988Focus on <i>RAS</i> Codon 61 Mutations in Metastatic Colorectal Cancer: A Retrospective AnalysisFrancesco Schietroma0Annunziato Anghelone1Giustina Valente2Viria Beccia3Giulia Caira4Alexia Spring5Giovanni Trovato6Armando Di Bello7Anna Ceccarelli8Laura Chiofalo9Serena Perazzo10Maria Bensi11Angelo Minucci12Andrea Urbani13Luigi Maria Larocca14Michele Basso15Carmelo Pozzo16Lisa Salvatore17Maria Alessandra Calegari18Giampaolo Tortora19Medical Oncology, Università Cattolica del Sacro Cuore, 00168 Roma, ItalyMedical Oncology, Università Cattolica del Sacro Cuore, 00168 Roma, ItalyMedical Oncology, Università Cattolica del Sacro Cuore, 00168 Roma, ItalyMedical Oncology, Università Cattolica del Sacro Cuore, 00168 Roma, ItalyMedical Oncology, Università Cattolica del Sacro Cuore, 00168 Roma, ItalyMedical Oncology, Università Cattolica del Sacro Cuore, 00168 Roma, ItalyMedical Oncology, Università Cattolica del Sacro Cuore, 00168 Roma, ItalyMedical Oncology, Università Cattolica del Sacro Cuore, 00168 Roma, ItalyMedical Oncology, Università Cattolica del Sacro Cuore, 00168 Roma, ItalyMedical Oncology, Università Cattolica del Sacro Cuore, 00168 Roma, ItalyMedical Oncology, Università Cattolica del Sacro Cuore, 00168 Roma, ItalyMedical Oncology, Università Cattolica del Sacro Cuore, 00168 Roma, ItalyDepartmental Unit of Molecular and Genomic Diagnostics, Genomics Core Facility, Gemelli Science and Technology Park (G-STeP), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, ItalyClinical Chemistry, Biochemistry and Molecular Biology Operations, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, ItalyPatologia Oncoematologica, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, ItalyMedical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, ItalyMedical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, ItalyMedical Oncology, Università Cattolica del Sacro Cuore, 00168 Roma, ItalyMedical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, ItalyMedical Oncology, Università Cattolica del Sacro Cuore, 00168 Roma, Italy<i>RAS</i> mutations involving codon 61 are rare in metastatic colorectal cancer (mCRC), accounting for only 1–4%, 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 <i>RAS</i>-mutated mCRC. Fifty patients with codon 61 <i>RAS</i>-mutated mCRC treated at our institution between January 2013 and December 2021 were enrolled. Additional datasets of codon 61 <i>RAS</i> 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 <i>RAS</i>-mutated mCRC compared to codon 61 <i>RAS</i> wild-type (54 vs. 28.5%), non-codon 61 <i>RAS</i>-mutated (35.6%), <i>BRAF</i> V600E-mutated (25%), and <i>RAS</i>/<i>BRAF</i> wild-type (20.5%) cohorts. At a median follow up of 96.2 months, the median OS for codon 61 <i>RAS</i>-mutated patients was significantly shorter compared to <i>RAS</i>/<i>BRAF</i> wild-type (26.9 vs. 36.0 months, HR 0.56) patients, while no significant difference was observed compared to non-codon 61 <i>RAS</i>-mutated and <i>BRAF</i> V600E-mutated patients. We showed a negative prognostic impact and a statistically significant correlation between codon 61 <i>RAS</i> mutations and metastatic involvement of the peritoneum and ovary.https://www.mdpi.com/2072-6694/16/5/988colorectal adenocarcinomaRASmetastatic colorectal cancerRAS signalingCodon 61MAPK pathway |
| spellingShingle | Francesco Schietroma Annunziato Anghelone Giustina Valente Viria Beccia Giulia Caira Alexia Spring Giovanni Trovato Armando Di Bello Anna Ceccarelli Laura Chiofalo Serena Perazzo Maria Bensi Angelo Minucci Andrea Urbani Luigi Maria Larocca Michele Basso Carmelo Pozzo Lisa Salvatore Maria Alessandra Calegari Giampaolo Tortora Focus on <i>RAS</i> Codon 61 Mutations in Metastatic Colorectal Cancer: A Retrospective Analysis Cancers colorectal adenocarcinoma RAS metastatic colorectal cancer RAS signaling Codon 61 MAPK pathway |
| title | Focus on <i>RAS</i> Codon 61 Mutations in Metastatic Colorectal Cancer: A Retrospective Analysis |
| title_full | Focus on <i>RAS</i> Codon 61 Mutations in Metastatic Colorectal Cancer: A Retrospective Analysis |
| title_fullStr | Focus on <i>RAS</i> Codon 61 Mutations in Metastatic Colorectal Cancer: A Retrospective Analysis |
| title_full_unstemmed | Focus on <i>RAS</i> Codon 61 Mutations in Metastatic Colorectal Cancer: A Retrospective Analysis |
| title_short | Focus on <i>RAS</i> Codon 61 Mutations in Metastatic Colorectal Cancer: A Retrospective Analysis |
| title_sort | focus on i ras i codon 61 mutations in metastatic colorectal cancer a retrospective analysis |
| topic | colorectal adenocarcinoma RAS metastatic colorectal cancer RAS signaling Codon 61 MAPK pathway |
| url | https://www.mdpi.com/2072-6694/16/5/988 |
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