KRAS and NRAS mutational gene profile of metastatic colorectal cancer patients in Jordan

Awidi, Muhammad; Ababneh, Nidaa A.; Shomaf, Maha; Fararjeh, Feras Al; Owaidi, Laila; AlKhatib, Mohammad Ahmad; Tarawneh, Buthaina; Awidi, Abdalla

doi:10.1371/journal.pone.0226473

Cited by 12 publications

(27 citation statements)

References 27 publications

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“…Additionally, similar to the results of other authors [24,25] we noticed that mutations G12D and G12V are the most prevalent in the Serbian population. We found that the frequency of mutations in codons 59, 117 and 146 were 1.5%, which is in concordance with the study of Awidi et al [26] while a higher prevalence of the mutation in codon 146 was observed in patients from Thailand, where 8.3% of them had this mutation [27]. Many authors evaluated correlations between mutations in KRAS, age and sex of patients with clinicopathological characteristics of CRC and some of the results indicate that both tumor location and KRAS status play important roles in the prognosis of CRC patients [19,20,28].…”

Section: Discussionsupporting

confidence: 93%

Mutations in the KRAS gene as a predictive biomarker of therapeutic response in patients with colorectal cancer

Jugović

Nikolić

Madić

et al. 2021

Revista Romana De Medicina De Laborator

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Introduction: Despite the important role of general KRAS mutational status in the selection of an adequate therapeutic protocol in patients with colorectal cancer (CRC), studies that focus on its specific mutations and their significance on progression of disease are scarce. This study aimed to determine the significance of specific KRAS mutations in response to standard chemotherapy protocols with oxaliplatin-based (FOLFOX 4, OXFL) in the first-line and irinotecan-based chemotherapy (FOLFIRI, IFL) in the second-line therapy, and to evaluate the correlation between these mutations and clinicopathological characteristics of CRC patients. Methods: Genomic DNA was extracted from the FFPE tumour tissue sections while the KRAS mutation test was performed by using PCR methods. Results: Prevalence of KRAS gene mutations in CRC patients was 45%. Mutated KRAS was more frequent in later stages of tumor infiltrations (P =0.0017), on the right side of the colon (P= 0.0044), and in patients who developed metastases in the first 6 months after CRC diagnosis than in patients who developed metastases after 24 months (P=0.0083). In a group of patients with a poor therapeutic response to standard chemotherapy the most frequent mutations in KRAS gene were G12D and G12V (63.88%), while in a group of patients with a good response to therapeutic protocols the most prevalent mutation was G12A (66.66%). Conclusion: Our results indicate that there was a significant difference in biological behaviour between tumours harboring different mutations in KRAS gene. Overall, mutation G12A could be a novel prognostic biomarker for CRC patients treated with standard chemotherapy.

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Section: Discussionsupporting

confidence: 93%

Mutations in the KRAS gene as a predictive biomarker of therapeutic response in patients with colorectal cancer

Jugović

Nikolić

Madić

et al. 2021

Revista Romana De Medicina De Laborator

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“…36 Other cohort studies have demonstrated similar results which are consistent with our findings. 37,38 While KRAS G12D mutation has been consistently reported to be the most common KRAS mutation, KRAS G12C mutation, which is now potentially amenable to pharmacotherapy, 39 accounts for 4% of mutations in our study. BRAF is the most frequently mutated protein kinase of the RAF family, accounting for about 10% of metastatic colorectal cancer.…”

Section: Discussionmentioning

confidence: 71%

Clinical and molecular profile of young adults with early‐onset colorectal cancer: Experience from four Australian tertiary centers

Siu

Ali

Tjokrowidjaja

et al. 2022

Asia-Pac J Clncl Oncology

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Background Patients with early‐onset colorectal cancer (EO‐CRC) have unique characteristics. Contemporary data on the pathological and molecular features, and survival of EO‐CRC are limited in the Australian context. Aim To determine the demographic, histopathological and molecular characteristics of adults with EO‐CRC, and their survival. Methods We conducted a retrospective study of adults aged 18–49 years with EO‐CRC who were referred to the Illawarra Shoalhaven Local Health District, South Eastern Sydney Local Health District and Royal North Shore Hospital in New South Wales, Australia, between 2014 and 2018. Results Of 257 patients included, 94 (37%) patients presented with de novo metastatic CRC, 80% patients had near‐average risk family history and 89% had a symptomatic presentation. In 159 patients with nonmetastatic disease at diagnosis, stage III disease (OR 3.88 [95% CI: 1.13–13.3]; p = .03) and the presence of perineural invasion (PNI) (OR 6.63 [95% CI: 2.21–19.84]; p = .001) were risk factors associated with the development of metastatic disease. Among 94 patients with de novo metastatic disease, 43 (43%) and 12 (14%) patients harbored a KRAS or BRAF V600E mutation, respectively. The median overall survival was 29.6 months (95% CI: 20.4–38.7). BRAF mutation was associated with inferior survival (HR 3.00 [95% CI: 1.30–6.94]; p = .01). Conclusion The prevalence of KRAS and BRAF mutations in our cohort is similar to the overseas experience. Stage III disease at diagnosis, presence of PNI and BRAF mutation are adverse prognostic indicators. A better understanding of the molecular landscape is needed for this patient cohort, so as to better tailor prevention strategies, screening and treatment pathways.

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“…(6,5%), G12S (3,3%), G12C (2,2%), K117N or A146V (10,85%) and Q61X (5,4%) (Awidi et al, 2019). In a study conducted by Baskin and colleagues in 2014, ratio of KRAS mutations in codon 12 and codon 13 were evaluated (Baskin et al, 2014).…”

Section: Findings and Discussionmentioning

confidence: 99%

Kolon Adenokarsinomlarında KRAS Mutasyon Durumunun Klinik Veriler ile Karşılaştırılması

BOYLU

Türkmen

2021

Karadeniz Fen Bilimleri Dergisi

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KRAS mutations are mutually exclusive with other activating mutations on EGFR pathway. Detection of KRAS mutations associated with tumorigenesis, predicates the lack of other mutations on the same pathway and shows that the application of targeted therapy approaches which target other proteins in EGFR-MAPK pathway ineffective. In this study, frequency of KRAS mutations in colorectal cancer and relationship between KRAS mutation status and other clinical features were assessed. KRAS mutations were detected in 47,7% of the cases included in our study. We determined that 76% of the mutations were located in codon 12, 9% of the mutations were located in codon 13, 9% of the mutations were located in codon 61 and 6% of the mutations located in codon 117 or codon 146. Determination of mutation rates and association of mutations with clinical features for different populations are important for planning of the treatment strategies nationwide. In our study, we have demonstrated that KRAS mutation status and clinical features associated with KRAS mutation is in accordance with the literature. We have determined that there is statistically significant correlation between grade and KRAS mutation status.

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KRAS and NRAS mutational gene profile of metastatic colorectal cancer patients in Jordan

Cited by 12 publications

References 27 publications

Mutations in the KRAS gene as a predictive biomarker of therapeutic response in patients with colorectal cancer

Mutations in the KRAS gene as a predictive biomarker of therapeutic response in patients with colorectal cancer

Clinical and molecular profile of young adults with early‐onset colorectal cancer: Experience from four Australian tertiary centers

Kolon Adenokarsinomlarında KRAS Mutasyon Durumunun Klinik Veriler ile Karşılaştırılması

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