Clinicopathological characteristics and mutational profile of KRAS and NRAS in Tunisian patients with sporadic colorectal cancer

Ounissi, Donia; Weslati, Marwa; Hazgui, Meriam; Bouraoui, Saâdia

doi:10.3906/sag-2003-42

Cited by 6 publications

(19 citation statements)

References 57 publications

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“…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 – 23 ], Tunisia ( n = 8) [ 24 – 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 – 23 ], 641 (34.8%) in Tunisia [ 24 – 31 ], 592 (32.1%) in Algeria [ 32 , 33 ], and 34 (1.8%) in Libya [ 34 ].…”

Section: Resultsmentioning

confidence: 99%

“…The retrieved articles describe studies conducted in Morocco ( n = 6) [ 18 – 23 ], Tunisia ( n = 8) [ 24 – 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 – 23 ], 641 (34.8%) in Tunisia [ 24 – 31 ], 592 (32.1%) in Algeria [ 32 , 33 ], and 34 (1.8%) in Libya [ 34 ]. The average age of patients was 52.7 years old [ 18 – 20 , 22 – 28 , 31 – 33 ], with 45.1% (260/577) [ 18 , 20 , 26 , 29 , 34 ] of patients diagnosed above the age of 50 years.…”

Section: Resultsmentioning

confidence: 99%

“…From the specimens where tumor site information was available, 31.4% (344/1095) of them were in the rectum [ 22 , 23 , 26 , 28 , 29 , 31 – 34 ], 30.1% (188/625) were in the right colon [ 18 , 22 , 24 , 25 , 28 , 31 ], and 56.5% (353/625) in the left colon [ 18 , 22 , 24 , 25 , 28 , 31 ]. The predominant histopathological type of CRC is adenocarcinoma (82.2%, 374/455) [ 18 , 20 , 25 ].…”

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%

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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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“…Colorectal cancer (CRC) is one of the leading reasons of cancer death among both men and women in Western World and the risk is increased with the effects of external factors such as consumption of alcohol, red meat, high fat and low fi ber food and sedentary lifestyle (1)(2). CRC comprises nearly 11 % of all diagnosed cancer types worldwide and approximately 1.800.000 new cases occur annually (3)(4). Early cancer diagnosis is an important step to qualify patients for surgical resection which is restricted with small percentage of patients and only a palliative approach in case of metastases.…”

Section: Introductionmentioning

confidence: 99%

Predictive value of KRAS/NRAS, IL-4 VNTR and HPV alterations in metastases of colorectal cancer

OZEN¹,

YEGIN²,

AVSAR³

et al. 2022

BLL

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PURPOSE:The main aim of the study was to evaluate the potential roles of KRAS/NRAS proto-oncogenes, IL-4 VNTR variants and HPV prevalence in colorectal cancer metastasis. As the second aim, the interactions of the analyzed genes and viral sequences with both clinicopathological variables and each other were targeted. METHODS: DNA was extracted using AmoyDx FFPE DNA Extraction kit from paraffi n-embedded colorectal tumor tissue samples (n = 60). NRAS/KRAS mutational profi les were determined with real-time polymerase chain reaction using AmoyDx KRAS/NRAS Mutation Detection Kit. Genotyping of IL-4 VNTR was made with PCR. HPV detection was analyzed by PCR with both GP5+/GP6+ consensus primers and type-specifi c primers for HPV-16 and HPV-18. SPSS v22 (IBM) statistics software was used for all statistical analyses. RESULTS: From the demographical/clinicopathological parameters, age and biopsy specimens revealed an association with metastasis. KRAS mutation rate was as high as 65 % in the patients and the most prevalent mutation type was G12D. Metastasis risk was 3.19-fold increased in KRAS-mutated patients compared to KRAS-negative ones. IL-4 VNTR genotypes/alleles were not associated with metastasis in our analysis. The frequency of HPVs in our colorectal cancer cohort was 36.7 %, but HPV positivity was not found to be associated with metastasis. A signifi cant association was found between HPV and NRAS mutations; NRAS wild-type status acted as a protective factor by 7.5-fold for HPV negativity. CONCLUSION: Our study comprehensively and concomitantly evaluated several potential molecular risk factors. Future studies designed in such combined approaches will substantially contribute to better manage colorectal cancer tumorigenesis from molecular biological perspective (Tab. 6, Fig. 2, Ref. 40).

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“…In CRC, mutations of KRAS in codon 12 is the most common mutation. 4 Surgery, chemotherapy and targeted therapies are used in the treatment of colorectal cancer. Targeted therapies are an effective alternative for patients have unresectable tumors.…”

Section: Introductionmentioning

confidence: 99%

The Mutation Profiles of K-RAS/N-RAS Genes in Metastatic Colorectal Cancer Patients

Keskin

Guzdolu

Sertdemir³

et al. 2022

Kocaeli Üniversitesi Sağlık Bilimleri Dergisi

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Amaç: RAS genleri, Epidermal Büyüme Faktörü Reseptörü (EGFR) tarafından indüklenen RAS-MAPK Sinyal yolağının bir üyesidir. Bu yolaktaki genlerde meydana gelen mutasyonlar kanser gelişimini tetiklemektedir. Kolorektal kanserde (KRK), RAS genlerinde meydana gelen mutasyonlar EGFR hedefli tedaviye karşı direnç gelişimine neden olur. EGFR monoklonal antikorları, kemoterapötik ajanlar olarak metastatik kolorektal kanser tedavisinde yaygın şekilde kullanılmaktadır. KRAS mutasyonları KRK’nın 30-50%’sinde, NRAS mutasyonları ise 2-3%’ünde bulunur. Bu çalışmada, KRK’lı hastalarda KRAS/NRAS mutasyonlarını analiz etmeyi amaçladık. Yöntem: EGFR-hedefli tedaviye direnç gösteren 100 metastatik KRK hastası, Real-Time Polimeraz Zincir Reaksiyonu yöntemi ile KRAS mutasyonu (ekzon 2, 3, 4) ve NRAS mutasyonu (ekzon 2, 3, 4) durumu için tarandı. Bulgular: Bu çalışma sonucunda, KRAS mutasyonu oranı 48% ve NRAS mutasyonu oranı 1,92% olarak bulundu. En yaygın KRAS mutasyonları kodon 12’de saptandı. Kodon 12 mutasyonlarının dağılımı G12V (25%), G12D (23%), G12C (14,5%) olarak elde edildi. Sonuç: Çalışmamızda saptanan KRAS ve NRAS mutasyon sıklıkları benzer raporlar ile uyumlu bulundu. Sonuçlarımız, RAS mutasyonlarının test edilmesinin EGFR-hedefli tedaviden fayda sağlayacak hastaları belirlemede hayati rolünü desteklemektedir.

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Clinicopathological characteristics and mutational profile of KRAS and NRAS in Tunisian patients with sporadic colorectal cancer

Cited by 6 publications

References 57 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

Predictive value of KRAS/NRAS, IL-4 VNTR and HPV alterations in metastases of colorectal cancer

The Mutation Profiles of K-RAS/N-RAS Genes in Metastatic Colorectal Cancer Patients

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