P-265 The study of mutations of the KRAS, NRAS, and BRAF genes in patients with colorectal cancer depending on gender, age, race in the population of the Republic of Kazakhstan

Smagulova, K.; Ukolova, Yelena; Kurmankulova, A.

doi:10.1016/j.annonc.2020.04.347

Cited by 2 publications

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“…For instance, Africans have a 21% frequency of CRCs with KRAS mutations, 22 a higher detection rate of KRAS mutation (54.4%) in Europeans CRC patients, while Asians predominantly have wt KRAS (51.4%) in CRC patients. 23 A study on mCRC patients in Jordan showed a distinct mutational profile with a higher frequency of KRAS (83.69%) and NRAS (6%) mutations compared to Western populations, suggesting an ethnic influence. 24 …”

Section: Discussionmentioning

confidence: 98%

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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Section: Discussionmentioning

confidence: 98%

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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“…An analysis of the relationship between mutations and race revealed the predominance of the wt in the Asian group (51.4%). In Europeans, the KRAS gene mutation was more often detected (54.4%) CRC patients (Smagulova et al, 2020). Colon cancers in Asians had a lower rate of KRAS mutations than blacks or whites (Yoon et al, 2015).…”

Section: Kras Nras and Braf Mutations In North Africamentioning

confidence: 97%

Clinical Significance of Somatic Mutations in RAS/RAF/MAPK Signaling Pathway in Moroccan and North African Colorectal Cancer Patients

Benmokhtar

Laraqui

Boukhrissi

et al. 2022

Asian Pac J Cancer Prev

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Background: Mutations in RAS (KRAS, NRAS) and BRAF genes are the main biomarker predicting response to anti-EGFR monoclonal antibodies in targeted therapy in colorectal cancer (CRC). Objective: Our study aims to evaluate the frequencies of KRAS, NRAS and BRAF mutations and their possible associations with clinico-pathological features in CRC patients from Morocco. Methods: DNA was extracted from 80 FFPE samples using the QIAamp DNA FFPE-kit. RAS and BRAF mutations were assessed by pyrosequencing assays using Qiagen, KRAS Pyro®kit 24.V1, Ras-Extension Pyro®kit 24.V1 and BRAF Pyro®Kit 24.V1, respectively, and carried out in the PyroMark-Q24. Results: RAS mutations were identified in 57.5% (56.2% in KRAS, 8.8% in NRAS). In KRAS gene, exon 2 mutations accounted for 93.3% (68.9% in codon 12, 24.4% in codon 13). Within codon 12, G12D was the most prevalent mutation (37.7%), followed by G12C (13.4%), G12S (8.9%) and G12V (6.6%). Within codon 13, the most frequently observed mutation was G13D (22.3%). The mutation rates of exon 3 and 4 were 15.6% and 13.3%, respectively. In exon 3 codon 61, 2.3% patients were detected with two concurrent mutations (Q61R, Q61H), and 4.4% with three concurrent mutations (Q61R, Q61H, Q61L). In NRAS gene, the mutation rates of exon 2, 3 and 4 were 57.1%, 28.6%, and 14.3%, respectively. G13A and Q61H were the most common mutations, accounting for 42.9% and 28.5%, respectively. There were 13% patients with concurrent KRAS/NRAS mutation and 4.3% wt KRAS with NRAS mutations. No mutations were identified in BRAF gene. In both sexes, KRAS codon 12 mutations were associated with higher stage III/IV tumors. Moreover, Patients whose tumor is in the proximal colon (56.3%) are more likely to harbor KRAS mutations than those tumor located in rectum (25%). Conclusion: RAS mutations could be useful in future target anti-EGFR therapy and molecular CRC screening strategy in Morocco.

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P-265 The study of mutations of the KRAS, NRAS, and BRAF genes in patients with colorectal cancer depending on gender, age, race in the population of the Republic of Kazakhstan

Cited by 2 publications

References 0 publications

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

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

Clinical Significance of Somatic Mutations in RAS/RAF/MAPK Signaling Pathway in Moroccan and North African Colorectal Cancer Patients

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