Positive Correlation Between Somatic Mutations in RAS Gene and Colorectal Cancer in Telangana Population: Hospital-Based Study in a Cosmopolitan City

Goud, Kalal Iravathy; Matam, Kavitha; Madasu, Adi Mahalakshmi; Khan, Imran Ali

doi:10.1007/s12010-019-03119-6

Cited by 6 publications

(4 citation statements)

References 30 publications

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“…In this study, we analyzed KRAS mutations in patients with mCRC: those occurring in exon 2 and outside of exon 2. The incidence of KRAS mutations in our study was approximately 48%, which is in line with what has been reported in a previous study in Jordan and other previous studies [20] [21,22] The majority of mutations fell in the KRAS exon 2 and constituted about 84% of the mutated cases. The frequencies of mutations in codon 12 and 13 were approximately 82% and 17% respectively.…”

Section: Discussionsupporting

confidence: 93%

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

et al. 2019

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BackgroundA constitutively active RAS protein in the absence of stimulation of the epidermal growth factor receptor (EGFR) is the result of mutations in KRAS and NRAS genes. Mutations in the KRAS exon 2 and outside exon 2 have been found to predict the resistance to anti-EGFR monoclonal therapy. A substantial proportion of metastatic colorectal cancer cases (mCRC) exhibit RAS mutations outside KRAS exon 2, particularly in KRAS exon 3 and 4 and NRAS exons 2 and 3. No data about RAS mutations outside KRAS exon 2 are available for Jordanian patients with mCRC. We aim to study the molecular spectrum, frequency, and distribution pattern of KRAS and NRAS mutations in Jordanian patients with mCRC.MethodsA cohort of 190 Jordanian metastatic colorectal cancer patients were enrolled in the trial. We detected mutations in exon 2 of the KRAS and NRAS gene as well as mutations outside of exon 2 using the StripAssay technique. The KRAS StripAssay covered 29 mutations and 22 NRAS mutations.ResultsMutations were observed in 92 (48.42%) cases, and KRAS exon 2 mutations accounted for 76 cases (83.69%). KRAS G12D was the most common mutation, occurring in 18 cases, followed by KRAS G12A in 16 cases, and G12T in 13 cases. Mutations outside of KRAS exon 2 represented 16.3% of the mutated cases. Among those, 6 cases (6.48%) carried mutations in NRAS exon 2 and 3, and 10 cases (10.87%) in KRAS exon 3 and 4.ConclusionThe frequency of NRAS and KRAS mutations outside of exon 2 appears to be higher in Jordanian patients in comparison with patients from western countries. KRAS mutations outside of exon 2 should be tested routinely to identify patients who should not be treated with anti-EGFR antibodies.

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Section: Discussionsupporting

confidence: 93%

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

et al. 2019

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“…The different bibliographic works report that KRAS mutations concern up to 89% of exon 2. This was well confirmed in our series where exon 2 mutations reached 87.3% [9]. Some studies have shown that mutations outside exon 2 are associated with shorter overall survival and relapse-free survival with Panitumumab-FOLFOX4-based therapy.…”

Section: Discussionsupporting

confidence: 89%

“…KRAS mutations would be more present in metastatic CRC, which aligns with the fact that KRAS mutations are of poor prognosis in CRC [12]. In the literature, it has been shown that mutated KRAS status correlates with female gender, distal colon, moderate degree of differentiation, presence of neoplastic vascular emboli and advanced TNM stage [9,12].…”

Section: Discussionmentioning

confidence: 61%

“…Additionally, the investigation for mutations in these sites revealed the presence of two heterozygous mutations: G12D at codon 12 and G13D at codon 13. For these latter mutations, it has already been established that Erlotinib/Gefitinib treatments, which are EGFR-TKIs (tyrosine kinase inhibitor), are not effective in metastatic colorectal cancer [9].…”

Section: Discussionmentioning

confidence: 99%

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"RAS Mutations in Colorectal Cancer in Tunisian Population"

Sahraoui¹

2022

BJSTR

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Background: Colorectal cancer (CRC) is the third most common cancer worldwide. Anti-EGFR therapy is currently one of the targeted therapies for metastatic CRC. Mutations in the RAS gene are predictive of poor response to anti-EGFR. Approximately 50-60% of CRCs have a RAS mutation with KRAS being the most frequently mutated gene. We aimed to analyse RAS mutations, using Idylla KRAS and NRAS mutation test, in CRC to determine the group of patients potentially candidates for anti-EGFR therapy. Besides, we tried to identify statistically significant associations between some clinicopathological parameters and the different types of KRAS mutations detected. Methods: A series of 119 cases of CRC was enrolled the Pathology department of Salah Azaiez Institute of Tunis from 02 April 2021 to 01 November 2021. Idylla KRAS and NRAS mutation test detected 21 mutations on the KRAS gene (exons 2, 3 and 4) and 18 mutations on the NRAS gene (exons 2, 3 and 4).Results: RAS gene mutations were found in 54% of cases, mainly of KRAS type (98.4%). For KRAS mutations, exon 2 mutations were found in 87.3%, followed by exon 4 (8%) and exon 3 (4.7%). Mutations in exon 2 involved codon 12 (56% G12D, 23.2% G12V, 9.3% G12C, 4.6% G12A, 4.6% G12S, 2.3% G12R) in 68% and codon 13 (G13D then G13V) in 32%. Mutations in exon 3 concerned codon 61 (the Q61H mutation followed by the Q61RL mutation). Mutations in exon 4 affected codon 146 (the A146P/T/V mutation). The only NRAS mutation found was a G12D mutation. Our work revealed that statistically, the presence of KRAS mutations was significantly associated to male patients (p=0.03) on one hand and to the presence of distant metastasis (p=0.03) on the other hand. Conclusion:Ras gene mutations seem to play a pivotal role in the resistance to anti-EGFR monoclonal antibodies in CRC treatments. Thus, testing for these mutations has become essential to select eligible candidates to benefit from this targeted therapy without unwarranted toxicity and expenses.

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