Mutation Analysis Of Kras And Braf Hotspots In Moroccan Patients With Colorectal Cancer

Jadda, Hajar

doi:10.5339/qfarf.2013.biosp-09

Cited by 5 publications

(16 citation statements)

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“…KRAS mutations in exon 2 codon 12 and 13 have been assessed in the most of the studies (94.1%, 16/17) [ 18 – 30 , 32 – 34 ]. BRAF gene mutation was analyzed in 41.2% (7/17) studies [ 18 , 19 , 21 – 23 , 31 , 33 ].…”

Section: Resultsmentioning

confidence: 99%

“…As seen in Table 5 , the G12D was the most frequently identified exon 2 mutations (31.6%, 137/433) [ 18 , 20 – 27 , 29 , 33 , 34 ], followed by G12V (25.4%, 110/433) [ 18 , 20 – 26 , 29 , 33 , 34 ], G13D (15.5%, 67/433) [ 18 , 20 – 27 , 29 , 33 , 34 ], G12C (10.2%, 44/433) [ 18 , 20 – 27 , 29 , 33 , 34 ], G12A (6.9%, 30/433) [ 18 , 20 – 22 , 24 , 27 , 29 , 33 ], G12S (6.4%, 28/433) [ 20 , 23 – 25 , 27 , 33 ]. G12R, G13V, G13C and G13R are less than 5% [ 18 , 20 , 21 , 24 – 26 ]. However, there are important differences among North Africa countries.…”

Section: Resultsmentioning

confidence: 99%

“…The total mutation frequency in the BRAF gene was 2.8% (17/602) [ 18 , 19 , 21 – 23 , 31 , 33 ]. The highest frequency of BRAF mutations was found in Tunisia and reported in 8.3% (4/48) of patients with CRC [ 31 ].…”

Section: Resultsmentioning

confidence: 99%

“…The highest frequency of BRAF mutations was found in Tunisia and reported in 8.3% (4/48) of patients with CRC [ 31 ]. The overall frequency of the BRAF V600E mutation was 2.8% (17/602) [ 18 , 19 , 21 – 23 , 31 , 33 ] (Tables 3 and 5 ).…”

Section: Resultsmentioning

confidence: 99%

“…The search of the databases yielded 17 relevant references which are closely related to defining the inclusion criteria and was included in this review. The retrieved articles describe studies conducted in Morocco (n = 6) [18][19][20][21][22][23], Tunisia (n = 8) [24][25][26][27][28][29][30][31], Algeria (n = 2) [32,33], and Libya (n = 1) [34]. A total of 1843 patients with CRC were included for our analysis, including 576 (31.3%) in Morocco [18][19][20][21][22][23], 641 (34.8%) in Tunisia [24][25][26][27][28][29][30][31], 592 (32.1%) in Algeria [32,33], and 34 (1.8%) in Libya [34].…”

Section: Resultsmentioning

confidence: 99%

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Prevalence and patterns of mutations in RAS/RAF/MEK/ERK/MAPK signaling pathway in colorectal cancer in North Africa

et al. 2022

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Background Our review discuss (i) the findings from analyzed data that have examined KRAS, NRAS and BRAF mutations in patients with colorectal cancer (CRC) in North Africa and to compare its prevalence with that shown in other populations and (ii) the possible role of dietary and lifestyle factors with CRC risk. Methods Using electronic databases, a systematic literature search was performed for the KRAS, NRAS, and BRAF mutations in CRC patients from Morocco, Tunisia, Algeria and Lybia. Results Seventeen studies were identified through electronic searches with six studies conducted in Morocco, eight in Tunisia, two in Algeria, and one in Libya. A total of 1843 CRC patients were included 576 (31.3%) in Morocco, 641 (34.8%) in Tunisia, 592 (32.1%) in Algeria, and 34 (1.8%) in Libya. Overall, the average age of patients was 52.7 years old. Patients were predominantly male (56.6%). The mutation rates of KRAS, NRAS and BRAF were 46.4%, 3.2% and 3.5% of all patients, respectively. A broad range of reported KRAS mutation frequencies have been reported in North Africa countries. The KRAS mutation frequency was 23.9% to 51% in Morocco, 23.1% to 68.2% in Tunisia, 31.4% to 50% in Algeria, and 38.2% in Libya. The G12D was the most frequently identified KRAS exon 2 mutations (31.6%), followed by G12V (25.4%), G13D (15.5%), G12C (10.2%), G12A (6.9%), and G12S (6.4%). G12R, G13V, G13C and G13R are less than 5%. There are important differences among North Africa countries. In Morocco and Tunisia, there is a higher prevalence of G12D mutation in KRAS exon 2 (≈50%). The most frequently mutation type in KRAS exon 3 was Q61L (40%). A59T and Q61E mutations were also found. In KRAS exon 4, the most common mutation was A146T (50%), followed by K117N (33.3%), A146P (8.3%) and A146V (8.3%). Conclusion KRAS mutated CRC patients in North Africa have been identified with incidence closer to the European figures. Beside established anti-CRC treatment, better understanding of the causality of CRC can be established by combining epidemiology and genetic/epigenetic on CRC etiology. This approach may be able to significantly reduce the burden of CRC in North Africa.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Prevalence and patterns of mutations in RAS/RAF/MEK/ERK/MAPK signaling pathway in colorectal cancer in North Africa

et al. 2022

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KRAS, NRAS and BRAF Mutational Profile of Colorectal Cancer in a Series of Moroccan Patients

El Zaitouni,

Laraqui,

Ghaouti

et al. 2024

Cancer Control

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Objectives The present study aimed to evaluate the frequencies of KRAS, NRAS, and BRAF mutations and their possible associations with clinicopathological features in 249 Moroccan patients with colorectal cancer (CRC). Methods A retrospective investigation of a cohort of formalin-fixed paraffin-embedded tissues of 249 patients with CRC was screened for KRAS/ NRAS/ BRAF mutations using Idylla™ technology and pyrosequencing. Results KRAS, NRAS, and BRAF mutations were revealed in 46.6% (116/249), 5.6% (14/249), and 2.4% (6/249) of patients. KRAS exon 2 mutations were identified in 87.9% of patients (102/116). KRAS G12D and G12 C were the most frequent, at 32.8% and 12.93%, respectively. Among the patients with KRAS exon 2 wild-type (wt), 27.6% (32/116) harbored additional KRAS mutations. Concurrent KRAS mutations were identified in 9.5% (11/116); including six in codon 146 (A146P/T/V), three in codon 61 (Q61H/L/R), one in codon 12 (G12 A and Q61H), and one in codon 13 (G13D and Q61 L). Among the NRAS exon 2 wt patients, 64.3% (9/14) harbored additional NRAS mutations. Concurrent NRAS mutations were identified in 28.6% (4/14) of NRAS-mutant patients. Since 3.2% wt KRAS were identified with NRAS mutations, concomitant KRAS and NRAS mutations were identified in 2.4% (6/249) of patients. KRAS mutations were higher in the >50-year-old age-group ( P = .031), and the tumor location was revealed to be significantly associated with KRAS mutations ( P = .028) predominantly in left colon (27.5%) and colon (42.2%) locations. NRAS mutations were most prevalent in the left colon (42.8%) and in well-differentiated tumors (64.2%). Conclusion Detection of KRAS mutations, particularly the G12 C subtype, may be significant for patients with CRC and has possible therapeutic implications. However, rare KRAS concomitant mutations in CRC patients suggest that each individual may present distinct therapeutic responses. KRAS testing alongside the identification of other affected genes in the same patient will make the treatments even more personalized by contributing more accurately to the clinical decision process. Overall, early diagnosis using novel molecular techniques may improve the management of CRC by providing the most efficient therapies for Moroccan patients.

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RAS/RAF/MAPK Pathway Mutations as Predictive Biomarkers in Middle Eastern Colorectal Cancer: A Systematic Review

Benmokhtar,

Laraqui,

Hilali

et al. 2024

Clin Med Insights Oncol

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Background: This review article aims to investigate the prevalence and spectrum of rat sarcoma (RAS) and V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) mutations, and their connection with geographical location, clinicopathological features, and other relevant factors in colorectal cancer (CRC) patients in the Middle East. Methods: A systematic literature review, employing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, was conducted to investigate the association between the frequency of relevant mutations and the descriptive clinicopathological characteristics of CRC patients. Multiple electronic databases, including PubMed, Science Direct, Web of Science, Scopus, and Google Scholar, were searched to analyze the relevant literature. Results: A total of 19 eligible studies comprising 2960 patients with CRC were included in this review. A comprehensive analysis of the collected literature data as well as descriptive and methodological insights is provided. Men were predominant in reviewed studies for the region, accounting for 58.6%. Overall, RAS mutation prevalence was 38.1%. Kirsten RAS Viral Oncogene Homolog (KRAS) mutations were the most common, accounting for 37.1% of cases and distributed among different exons, with the G12D mutation being the most frequent in exon 2 (23.2%) followed by G12V (13.7%), G13D (10.1%), G12C (5.1%), G12A (5.04%), and G12S (3.6%). Neuroblastoma RAS Viral Oncogene Homolog (NRAS) mutations were identified in 3.3% of tumor samples, with the most common mutation site located in exons 2, 3, and 4, and codon 61 being the most common location for the region. The total mutation frequency in the BRAF gene was 2.6%, with the V600E mutation being the most common. Conclusion: The distribution patterns of RAS and BRAF mutations among CRC patients exhibit notable variations across diverse ethnic groups. Our study sheds light on this phenomenon by demonstrating a higher prevalence of KRAS mutations in CRC patients from the Middle East, as compared with those from other regions. The identification of these mutations and geographical differences is important for personalized treatment planning and could potentially aid in the development of novel targeted therapies. The distinct distribution patterns of RAS and BRAF mutations among CRC patients across different ethnic groups, as well as the regional variability in mutation prevalence, highlight the need for further research in this area.

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Mutation Analysis Of Kras And Braf Hotspots In Moroccan Patients With Colorectal Cancer

Cited by 5 publications

References 0 publications

Prevalence and patterns of mutations in RAS/RAF/MEK/ERK/MAPK signaling pathway in colorectal cancer in North Africa

Prevalence and patterns of mutations in RAS/RAF/MEK/ERK/MAPK signaling pathway in colorectal cancer in North Africa

KRAS, NRAS and BRAF Mutational Profile of Colorectal Cancer in a Series of Moroccan Patients

RAS/RAF/MAPK Pathway Mutations as Predictive Biomarkers in Middle Eastern Colorectal Cancer: A Systematic Review

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