The mutational spectrum of NRAS gene discovers a novel frameshift mutation (E49R) in Saudi colorectal cancer patients
Abstract Colorectal cancer (CRC) is a major health problem the world face currently and one of the leading causes of death worldwide. CRC is genetically heterogeneous and multiple genetic aberrations may appear on course of the disease throughout patient’s lifetime. Genetic biomarkers such as BRAF,...
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| Format: | Article |
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BMC
2025-01-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-025-03652-x |
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| author | Mahmood Rasool Absarul Haque Mohammed Alharthi Abdulrahman Sibiany Mohammed Saad Alamri Samer Mohammed Hassan Alqarni Irfan A. Rather Adeel G. Chaudhary Sajjad Karim Peter Natesan Pushparaj |
| author_facet | Mahmood Rasool Absarul Haque Mohammed Alharthi Abdulrahman Sibiany Mohammed Saad Alamri Samer Mohammed Hassan Alqarni Irfan A. Rather Adeel G. Chaudhary Sajjad Karim Peter Natesan Pushparaj |
| author_sort | Mahmood Rasool |
| collection | DOAJ |
| description | Abstract Colorectal cancer (CRC) is a major health problem the world face currently and one of the leading causes of death worldwide. CRC is genetically heterogeneous and multiple genetic aberrations may appear on course of the disease throughout patient’s lifetime. Genetic biomarkers such as BRAF, KRAS, and NRAS may provide early precision treatment options that are crucial for patient survival and well-being. The aim of this study was to identify pathogenic mutations in the NRAS gene causing colorectal cancer in the Saudi population. We enrolled 80 CRC tumor tissue samples and performed molecular analyses to establish the mutation spectrum status in the western region of Saudi Arabia. We identified 5 different mutations in 10 patients, 4 of whom were reported previously (G10R, E37K, Q61K, and Q61*) in the literature while we discovered one novel lethal insertion mutation (E49R). A novel identified insertion mutation was present in the third codon of the NRAS gene [c.145 insA (p.Glu49ArgTer85)], causing a frameshift in the amino acid sequence of the protein, and leading to an aberrant and truncated protein of 85 amino acids. Subsequent bioinformatics analysis showed that the mutation was highly deleterious and affected protein function to a greater extent. This identification may further improve the prognosis of CRC and benefit subsequent treatment choices. |
| format | Article |
| id | doaj-art-f42b5955a33144e580b804d1b21bdfab |
| institution | Kabale University |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-f42b5955a33144e580b804d1b21bdfab2025-01-26T12:53:31ZengBMCCancer Cell International1475-28672025-01-0125111010.1186/s12935-025-03652-xThe mutational spectrum of NRAS gene discovers a novel frameshift mutation (E49R) in Saudi colorectal cancer patientsMahmood Rasool0Absarul Haque1Mohammed Alharthi2Abdulrahman Sibiany3Mohammed Saad Alamri4Samer Mohammed Hassan Alqarni5Irfan A. Rather6Adeel G. Chaudhary7Sajjad Karim8Peter Natesan Pushparaj9Institute of Genomic Medicine Sciences, King Abdulaziz UniversityKing Fahd Medical Research Center, Faculty of Applied Medical Sciences, King Abdulaziz UniversityFaculty of Medicine, King Abdulaziz University Hospital, King Abdulaziz UniversityFaculty of Medicine, King Abdulaziz University Hospital, King Abdulaziz UniversityDepartment of Biological Sciences, Faculty of Science, King Abdulaziz UniversityDepartment of Biological Sciences, Faculty of Science, King Abdulaziz UniversityDepartment of Biological Sciences, Faculty of Science, King Abdulaziz UniversityInstitute of Genomic Medicine Sciences, King Abdulaziz UniversityInstitute of Genomic Medicine Sciences, King Abdulaziz UniversityInstitute of Genomic Medicine Sciences, King Abdulaziz UniversityAbstract Colorectal cancer (CRC) is a major health problem the world face currently and one of the leading causes of death worldwide. CRC is genetically heterogeneous and multiple genetic aberrations may appear on course of the disease throughout patient’s lifetime. Genetic biomarkers such as BRAF, KRAS, and NRAS may provide early precision treatment options that are crucial for patient survival and well-being. The aim of this study was to identify pathogenic mutations in the NRAS gene causing colorectal cancer in the Saudi population. We enrolled 80 CRC tumor tissue samples and performed molecular analyses to establish the mutation spectrum status in the western region of Saudi Arabia. We identified 5 different mutations in 10 patients, 4 of whom were reported previously (G10R, E37K, Q61K, and Q61*) in the literature while we discovered one novel lethal insertion mutation (E49R). A novel identified insertion mutation was present in the third codon of the NRAS gene [c.145 insA (p.Glu49ArgTer85)], causing a frameshift in the amino acid sequence of the protein, and leading to an aberrant and truncated protein of 85 amino acids. Subsequent bioinformatics analysis showed that the mutation was highly deleterious and affected protein function to a greater extent. This identification may further improve the prognosis of CRC and benefit subsequent treatment choices.https://doi.org/10.1186/s12935-025-03652-xColorectal cancerNRAS geneNovel mutationGenetic landscape |
| spellingShingle | Mahmood Rasool Absarul Haque Mohammed Alharthi Abdulrahman Sibiany Mohammed Saad Alamri Samer Mohammed Hassan Alqarni Irfan A. Rather Adeel G. Chaudhary Sajjad Karim Peter Natesan Pushparaj The mutational spectrum of NRAS gene discovers a novel frameshift mutation (E49R) in Saudi colorectal cancer patients Cancer Cell International Colorectal cancer NRAS gene Novel mutation Genetic landscape |
| title | The mutational spectrum of NRAS gene discovers a novel frameshift mutation (E49R) in Saudi colorectal cancer patients |
| title_full | The mutational spectrum of NRAS gene discovers a novel frameshift mutation (E49R) in Saudi colorectal cancer patients |
| title_fullStr | The mutational spectrum of NRAS gene discovers a novel frameshift mutation (E49R) in Saudi colorectal cancer patients |
| title_full_unstemmed | The mutational spectrum of NRAS gene discovers a novel frameshift mutation (E49R) in Saudi colorectal cancer patients |
| title_short | The mutational spectrum of NRAS gene discovers a novel frameshift mutation (E49R) in Saudi colorectal cancer patients |
| title_sort | mutational spectrum of nras gene discovers a novel frameshift mutation e49r in saudi colorectal cancer patients |
| topic | Colorectal cancer NRAS gene Novel mutation Genetic landscape |
| url | https://doi.org/10.1186/s12935-025-03652-x |
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