Mutational spectrum of BRAF gene in colorectal cancer patients in Saudi Arabia.
PMID 34588906 | PMCID PMC8459112 | DOI 10.1016/j.sjbs.2021.06.048 · Saudi journal of biological sciences · 2021 · View on PubMed ↗
Colorectal cancer (CRC) is one of the topmost causes of death in males in Saudi Arabia. In females, it was also within the top five cancer types. CRC is heterogeneous in terms of pathogenicity and molecular genetic pathways. It is very important to determine the genetic causes of CRC in the Saudi population. BRAF is one of the major genes involved in cancers, it participates in transmitting chemical signals from outside the cells into the nucleus of the cells and it is also shown to participate in cell growth. In this study, we mapped the spectrum of BRAF mutations in 100 Saudi patients with CRC. We collected tissue samples from colorectal cancer patients, sequenced the BRAF gene to identify gene alterations, and analyzed the data using different bioinformatics tools. We designed a three-dimensional (3D) homology model of the BRAF protein using the Swiss Model automated homology modeling platform to study the structural impact of these mutations using the Missense3D algorithm. We found six mutations in 14 patients with CRC. Four of these mutations are being reported for the first time. The novel frameshift mutations observed in CRC patients, such as c.1758delA (E586E), c.1826insT (Q609L), c.1860insA and c.1860insA/C (M620I), led to truncated proteins of 589, 610, and 629 amino acids, respectively, and potentially affected the structure and the normal functions of BRAF. These findings provide insights into the molecular etiology of CRC in general and to the Saudi population. BRAF genetic testing may also guide treatment modalities, and the treatment may be optimized based on personalized gene variations.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | BRAF | “Mutational spectrum of BRAF gene in colorectal cancer patients in Saudi Arabia.” | 0.98 | hgnc_dict_v1 |
| phenotype | colorectal cancer | “Mutational spectrum of BRAF gene in colorectal cancer patients in Saudi Arabia.” | 0.98 | phenotype_alias_lexicon_v2 |
| population | Saudi Arabia | “Mutational spectrum of BRAF gene in colorectal cancer patients in Saudi Arabia. Colorectal cancer (CRC) is one of the topmost causes of death in males in Saudi Arabia. It is very important to determine the genetic causes of CRC in the Saudi population. In this study, we mapped the spectrum of BRAF mutations in 100 Saudi patients with CRC. These findings provide insights into the molecular etiology of CRC in general and to the Saudi population.” | 0.95 | saudi_context_rules_v1 |
| variant | c.1758delA | “The novel frameshift mutations observed in CRC patients, such as c.1758delA (E586E), c.1826insT (Q609L), c.1860insA and c.1860insA/C (M620I), led to truncated proteins of 589, 610, and 629 amino acids, respectively, and potentially affected the structure and the normal functions of BRAF.” | 0.95 | hgvs_regex_v1 |
| variant | c.1826insT | “The novel frameshift mutations observed in CRC patients, such as c.1758delA (E586E), c.1826insT (Q609L), c.1860insA and c.1860insA/C (M620I), led to truncated proteins of 589, 610, and 629 amino acids, respectively, and potentially affected the structure and the normal functions of BRAF.” | 0.95 | hgvs_regex_v1 |
| variant | c.1860insA | “The novel frameshift mutations observed in CRC patients, such as c.1758delA (E586E), c.1826insT (Q609L), c.1860insA and c.1860insA/C (M620I), led to truncated proteins of 589, 610, and 629 amino acids, respectively, and potentially affected the structure and the normal functions of BRAF.” | 0.95 | hgvs_regex_v1 |
| variant | E586E | “The novel frameshift mutations observed in CRC patients, such as c.1758delA (E586E), c.1826insT (Q609L), c.1860insA and c.1860insA/C (M620I), led to truncated proteins of 589, 610, and 629 amino acids, respectively, and potentially affected the structure and the normal functions of BRAF.” | 0.82 | literature_variant_regex_v2 |
| variant | Q609L | “The novel frameshift mutations observed in CRC patients, such as c.1758delA (E586E), c.1826insT (Q609L), c.1860insA and c.1860insA/C (M620I), led to truncated proteins of 589, 610, and 629 amino acids, respectively, and potentially affected the structure and the normal functions of BRAF.” | 0.82 | literature_variant_regex_v2 |
| variant | M620I | “The novel frameshift mutations observed in CRC patients, such as c.1758delA (E586E), c.1826insT (Q609L), c.1860insA and c.1860insA/C (M620I), led to truncated proteins of 589, 610, and 629 amino acids, respectively, and potentially affected the structure and the normal functions of BRAF.” | 0.82 | literature_variant_regex_v2 |