KRAS, NRAS, and BRAF mutation prevalence, clinicopathological association, and their application in a predictive model in Mexican patients with metastatic colorectal cancer: A retrospective cohort study

Sánchez-Ibarra, Héctor E.; Jiang, Xianli; Gallegos-Gonzalez, Elena Yareli; Cavazos-González, Adriana Carolina; Chen, Yenho; Morcos, Faruck; Barrera-Saldaña, Hugo A.

doi:10.1371/journal.pone.0235490

Cited by 28 publications

(30 citation statements)

References 38 publications

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“…The median age of onset of the disease in the included patients was 63.5 years, which corresponds to the data from other populations [23][24][25][26]. The majority (61.7%) of the patients were aged over 60 years, and only 2 (5.9%) patients were younger than 45 years old (Table 2).…”

Section: Discussionsupporting

confidence: 79%

Genetic and phenotypic characteristics of Russian patients with BRAF-mutated colorectal cancer

Логинова¹,

Shelygin²,

Vitaly³

et al. 2021

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Colorectal cancer (CRC) is one of the most common malignancies in the world. It's estimated about 1,8 M new CRC cases worldwide per year. A somatic mutation in the BRAF gene in the tumor is a negative prognostic factor. This work is aimed at studying the clinical and genetic characteristics of Russian CRC patients with the BRAF mutation. The BRAF mutations were studied by Sanger sequencing and digital droplet PCR in 489 patients and found in 34 (7%) cases. The most common mutation was p.V600E (82%). Also, rare variants were found: p.K601E, p.N581I, p.G596R, and p.D594N. All the patients with rare mutations were characterized by an unfavorable prognosis of the disease. The clinical features of the patients with BRAF mutations in the study include the predominant primary tumor site in the rectum, in addition to the right colon. Then, most of the cases were diagnosed in the advanced stages of the disease and were represented by high-grade adenocarcinomas. This article demonstrates the feasibility of analysis of the entire exon 15 of BRAF gene in CRC patients regardless of tumor localization.

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Section: Discussionsupporting

confidence: 79%

Genetic and phenotypic characteristics of Russian patients with BRAF-mutated colorectal cancer

Логинова¹,

Shelygin²,

Vitaly³

et al. 2021

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“…KRAS mutations occurred significantly more frequently in African Americans than Caucasians (37% vs. 21%, P = 0.01) and were associated with worse stage or grade of CRC [28] . It is noteworthy that such a difference is mainly caused by codon 12 mutations: indeed, many studies have reported that codon 12 mutations are significantly more frequent in African Americans than Caucasians (P = 0.04), whereas the frequencies of mutations in codon 13, exon 3, and exon 4 did not differ significantly according to ethnicity [27][28][29] . Interestingly, even within the same ethnic group, there can be differences.…”

Section: Kras Differences In the Heterogeneous American Populationmentioning

confidence: 97%

Research progress on KRAS mutations in colorectal cancer

Cefalì¹,

Epistolio²,

Palmarocchi³

et al. 2021

JCMT

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The RAS gene family, responsible for signal transduction within the mitogen activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K) pathways, is frequently involved in carcinogenesis, and alterations in its member genes can be detected, with variable frequency, in a wide variety of solid and hematological cancers. These alterations may behave as prognostic-predictive biomarkers and driver mutations, making them an interesting therapeutic target. Since their discovery, many strategies have been pursued to act on their signaling pathways. Indeed, in clinical practice, KRAS, the most prominent member of the RAS gene family, represents an especially elusive target in most malignancies; pathway inhibition is carried out upstream, on the EGFR receptor, or downstream, most frequently on the BRAF/MEK/ERK cascade. Recently, clinically relevant direct RAS inhibition has been successfully achieved with the development of potent and selective covalent inhibitors of KRAS c.34G>T (p.G12C). These latest-generation drugs represent both a new and interesting tool in the therapeutic armamentarium and a symbolic end to the myth of KRAS undruggability. However, their clinical relevance and appropriate place in treatment strategies remain to be determined.

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“…It has been presented that NRAS mutations are rare CRCs and do not appear to be associated with any of the molecular features, including mutation of KRAS , BRAF , PIK3CA , MSI, and CIMP [ 44 ]. Moreover, the frequency of double mutations involving NRAS mutations is rare [ 45 , 46 ]. Only three samples displayed triple mutations from the cases studied here (n = 2347), including NRAS , and analysis was impossible.…”

Section: Discussionmentioning

confidence: 99%

Frequency and Clinicopathological Characteristics of Patients With KRAS/BRAF Double-Mutant Colorectal Cancer: An In Silico Study

Uchida

Kojima²,

Sugino³

2022

Pathol. Oncol. Res.

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KRAS and BRAF mutations are currently thought to be mutually exclusive as their co-occurrence is extremely rare. Therefore, clinicopathological and molecular characteristics of colorectal carcinoma with KRAS/BRAF double mutations are unclear. We aimed to investigate the frequency and clinicopathological characteristics of double-mutant colorectal carcinoma and its differences from KRAS/BRAF single-mutant colorectal carcinoma using bioinformatics tools. We estimated the KRAS/BRAF double mutation frequency in the whole exon and coding sequences via bioinformatic analyses of three datasets from cBioPortal. We compared the clinicopathological characteristics, microsatellite instability status, BRAF classification, and tumor mutation burden of patients harboring the double mutants with those of patients harboring KRAS or BRAF single mutations. We integrated three large datasets and found that the frequency of the KRAS/BRAF double mutation in the dataset was 1.2% (29/2347). The double mutation occurred more frequently in males, with a slightly higher occurrence in the right side of the colon. Sex, histological type, histological grade, microsatellite instability, and tumor mutation burden of the patients harboring KRAS-mutant, BRAF-mutant, and double-mutant colorectal carcinoma varied significantly. The frequency of double-mutant colorectal carcinoma was 60 times higher than that previously reported. Significantly fewer double-mutant colorectal carcinoma cases were classified as BRAF class 1 and more were classified as unknown. Our findings indicate that the biological characteristics of double-mutant tumors are different from those of single-mutant tumors.

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KRAS, NRAS, and BRAF mutation prevalence, clinicopathological association, and their application in a predictive model in Mexican patients with metastatic colorectal cancer: A retrospective cohort study

Cited by 28 publications

References 38 publications

Genetic and phenotypic characteristics of Russian patients with BRAF-mutated colorectal cancer

Genetic and phenotypic characteristics of Russian patients with BRAF-mutated colorectal cancer

Research progress on KRAS mutations in colorectal cancer

Frequency and Clinicopathological Characteristics of Patients With KRAS/BRAF Double-Mutant Colorectal Cancer: An In Silico Study

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