Prevalence of KRAS mutations in metastatic colorectal cancer: A retrospective observational study from India

Veldore, VH; Rao, Rajesh P. N.; Prabhudesai, SA; Tejaswi, R; Kakara, S; Pattanayak, Shakti Prasad; Krishnamoorthy, Naveen; Bn, Tejaswini; Hazarika, Diganta; Gangoli, Aparna; Rahman, S.M. Jamshedur; Dixit, Jagannath V; Naik, Radheshyam; Diwakar, RB; Satheesh, C T; H, Shashidhara; Patil, Shekar; Ks, Gopinath; Kumar, B. Ajai

doi:10.4103/0019-509x.175371

Cited by 10 publications

(16 citation statements)

References 52 publications

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“…Similar to the findings in the Indian study reported by Veldore et al [7], no significant correlation was found between the KRAS genotypes and the patients’ age and gender in this study. However, significantly higher mutation rates in well-differentiated tumours and tumours located at the distal end of the colon were observed in the Indian cohort.…”

Section: Discussionsupporting

confidence: 90%

“…In contrast to these studies, the most common mutation identified in codon 12 in this study was p.Gly12Val (24.0%). A similar finding was observed in a retrospective study conducted among 299 patients with mCRC in India [7]. This may be a reflection of the genetic heterogeneity in the pattern of KRAS mutations in mCRC patients.…”

Section: Discussionsupporting

confidence: 86%

“…Some studies have reported significant differences between the KRAS genotypes and clinicopathological variables such as age, gender, tumour location, tumour histopathology, and metastasis while other studies observed no significant effects [7, 11]. Similar to the findings in the Indian study reported by Veldore et al [7], no significant correlation was found between the KRAS genotypes and the patients’ age and gender in this study.…”

Section: Discussionsupporting

confidence: 84%

“…Previous studies [2, 6, 7] have reported that the most common KRAS mutation types are p.Gly12Asp, p.Gly12Val and p.Gly13Asp, accounting for almost 70.0% of all mutations. Overall, a similar pattern was seen in this study where these 3 mutations accounted for 72.0% of all the KRAS mutations.…”

Section: Discussionmentioning

confidence: 99%

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The pattern of KRAS mutations in metastatic colorectal cancer: a retrospective audit from Sri Lanka

Sirisena

Deen

Mandawala³

et al. 2017

BMC Res Notes

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ObjectiveActivating mutations in the KRAS gene, found in approximately 53% of metastatic colorectal cancer (mCRC) cases, can render epidermal growth factor receptor (EGFR) inhibitors ineffective. Regional differences in these mutations have been reported. This is the first study which aims to describe the pattern of KRAS mutations in a Sri Lankan cohort of mCRC patients.ResultsThe KRAS genotypes detected in mCRC patients which have been maintained in an anonymized database were retrospectively analyzed. Of the 108 colorectal tissue samples tested, 25 (23.0%) had KRAS mutations. Overall, there were 68 (63.0%) males and 40 (37.0%) females. Among the KRAS positive cases, there were 14 (56.0%) males and 11 (44.0%) females. Their age distribution ranged from 29 to 85 years with a median age of 61 years. There were 15 patients (60.0%) with point mutations in codon 12 while 10 (40.0%) had a single mutation in codon 13. The most common KRAS mutation identified was p.Gly13Asp (40.0%), followed by p.Gly12Val (24.0%). Other mutations included p.Gly12Cys (12.0%), p.Gly12Ser (12.0%), p.Gly12Asp (8.0%), and p.Gly12Arg (4.0%). The codon 13 mutation was a G>A transition (40.0%), while G>T transversions (32.0%), G>A transitions (24.0%), and G>C transversions (4.0%) were found in the codon 12 mutations. The frequency of KRAS mutations was similar to that reported for Asian patients. However, in contrast to several published studies, the G>A transition in codon 12 (c.35G>A; p.Gly12Asp), was not the most common mutation within codon 12 in our cohort. This may be a reflection of the genetic heterogeneity in the pattern of KRAS mutations in mCRC patients but valid conclusions cannot be drawn from these preliminary findings due to the small size of the study sample.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

The pattern of KRAS mutations in metastatic colorectal cancer: a retrospective audit from Sri Lanka

Sirisena

Deen

Mandawala³

et al. 2017

BMC Res Notes

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“…When it comes to tumor location, disparities have been reported where KRAS mutation rates were higher in the right-sided CRC tumors [2,36,40,44]. Our study, along with others, showed an association rather with the left side of the colon [45][46][47][48].…”

Section: Discussionsupporting

confidence: 59%

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

et al. 2021

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Background/aim: Colorectal cancer (CRC) is a major public health problem worldwide and in Tunisia due to its increasing incidence. KRAS and NRAS mutations have become a pivotal part of CRC diagnosis, given their association to treatment resistance with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies. We aim to screen for mutations in KRAS and NRAS genes in Tunisian patients with CRC and to explore their correlations with clinicopathological features. Materials and methods: AmoyDx KRAS and NRAS mutation real-time PCR kits were used to screen for mutations in KRAS (exon 2) and NRAS (exons 2, 3 and 4) in 96 CRC tumors. Results: KRAS exon 2 mutations were found in 41.7% (40/96) of the patients. Codon 12 most abundant mutations were G12D and G12V followed by G12A, while G13D is the predominant mutation in codon 13. KRAS exon 2 mutations were associated with older patients (p = 0.029), left-sided tumors (p = 0.037) and greater differentiation (p = 0.044). The prevalence rate of NRAS mutations was 7.3%, mostly in exon 2. These mutations were associated with early stages (p = 0.039) and the absence of lymph node metastasis (p = 0.045). Conclusion: It can be inferred from this study that Tunisian CRC patients have a similar frequency of KRAS and NRAS mutations compared to those observed in other populations. Consequently, screening for KRAS and NRAS mutation is crucial to orientate the therapies and the selection of an appropriate candidate, avoiding patients' unnecessary toxicity and costs.

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Lesser prevalence of polyps/WNT‐dysregulation and concomitant upregulation of gamma‐catenin/MYC point to alternate pathways in colorectal cancer in India

Vishnubhotla,

Avanthi,

Mitnala

et al. 2023

Molecular Carcinogenesis

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Colorectal cancer (CRC) is known to follow adenoma carcinoma sequence (ACS) in majority of the tumors and the driver variants and associated pathways are well delineated. However, most of the published data are from the west and information in other ethnicities is sparse. We therefore comprehensively evaluated the CRC tumors from Indian ethnicity for the prevalence of ACS. In this cohort study, clinical data of 100,497 patients who attended hospital between 2013 and 2018 were accessed. Tumors from patients (n = 130) with CRC who were treated primarily by surgery were included. DNA and RNA were isolated to assess variants (direct sequencing) and WNT‐pathway dysregulation in genes related to ACS. Global gene expression was generated and analyzed on microarrays (Affymetrix; N = 10) and next generation sequencing platforms (Illumina; N = 25). Gene expression at mRNA (qRT‐PCR) and protein level (IHC) of JUP/CTNNB1/MYC were assessed. Correlation between expression of JUP and MYC was evaluated by Karl Pearson's correlation coefficient. The prevalence of polyps was 16.75%, while 18.26% variants in APC/CTNNB1, 20.00% in KRAS, and 18.33% WNT dysregulation were noted. Interestingly, 29/60 (48.33%) tumors showed only MYC upregulation with normal APC/CTNNB1 expression. Global gene expression and validation in an independent tumor cohort confirmed concomitant upregulation of JUP (gamma‐catenin) & MYC (r = 0.71; p = 0.001) at mRNA and protein in sizeable number of tumors (45/96; 46.88%). Our study provides evidence for limited prevalence of ACS in the Indian ethnicity. Preventive colonoscopies for early identification and management of CRC may not be an effective strategy in this ethnicity.

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Prevalence of KRAS mutations in metastatic colorectal cancer: A retrospective observational study from India

Cited by 10 publications

References 52 publications

The pattern of KRAS mutations in metastatic colorectal cancer: a retrospective audit from Sri Lanka

The pattern of KRAS mutations in metastatic colorectal cancer: a retrospective audit from Sri Lanka

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

Lesser prevalence of polyps/WNT‐dysregulation and concomitant upregulation of gamma‐catenin/MYC point to alternate pathways in colorectal cancer in India

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