Coexistence of KRAS and BRAF mutations in colorectal cancer: a case report supporting the concept of tumoral heterogeneity

The detection of KRAS and BRAF mutations is a crucial step for the correct therapeutic approach and predicting the epidermal growth factor receptor [EGFR]-targeted therapy resistance of colorectal carcinomas. The concomitant KRAS and BRAF mutations occur rarely in the colorectal cancers [CRCs] with the prevalence of less than 0.001% of the cases. In patients with KRAS-mutant tumors, BRAF mutations should not regularly be tested unless the patient is participating in a clinical trial enriching for the presence of KRAS or BRAF-mutated tumor. The current report demonstrates a case with advanced adenocarcinoma of the colon showing the coexistence of KRAS and BRAF mutations and may have profound clinical implications for disease progression and therapeutic responses

Lack of BRAF-V600E mutation in stage I and II of colorectal cancer

Aim: We aimed to explore the frequency of BRAF V600E mutation in Iranian patients with colorectal cancer [CRC] as well as its association with clinic pathological characteristic of patients

Background: CRC is the third leading cause of cancer related death. There is a growing body of data showing the association of BRAF V600E mutation with malignant transformation and clinical outcome of different tumors, including CRC. These findings suggest that BRAF V600E mutation can be used as diagnostic and/or prognostic biomarker for management of cancer patients

Patients and methods: A total of 85 patients with sporadic tumor were recruited. Braf V600E mutation was investigated using sequencing of extracted DNAs from formalin-fixed paraffin-embedded [FFPE] tumor tissues. Electropherograms were analyzed using Laser-gene 6 software

Results: More than 95% of patients were in stage I and II and none of them were in stage IV. Patients were mostly below 55 years old and tumors were dominantly located in the distal colon. Of note, no BRAF V600E mutations were detected in our population

Conclusion: Our results showed no V600E mutation in the BRAF gene in stage I and II of CRC patients. Further studies in multi-center settings are warranted to examine the prognostic and/or predictive value of this marker in different stages of colorectal cancer patients

Polymorphism of SMAD 7 gene [rs2337104] and risk of colorectal cancer in an Iranian population: a case-control study

The purpose of this study was to evaluate the influence of intronic polymorphism of the SMAD7 [Mothers Against Decantaplegic Homolog 7] gene [rs2337104] on the risk of colorectal cancer [CRC] and clinicopathological features in an Iranian population. SMAD7 has been identified as an antagonist of transforming growth factor beta [TGF-b]-mediating fibrosis, carcinogenesis, and inflammation. Regarding to the recent genome-wide scan, a risk locus for colorectal cancer at 18q21 has been found, which maps to the SMAD7 gene. This case-control study was performed on 109 CRC patients and 109 healthy controls recruited in Taleghani Hospital. The genotyping of all samples were done by TaqMan assay via an ABI 7500 Real Time PCR System [Applied Biosystems] with DNA from peripheral blood. The association of this polymorphism with the risk of CRC and clinico pathological features was investigated. Our results indicated that there were no significant association between genotypic and allelic frequencies of SMAD7 polymorphism [rs2337104] and CRC risk in our population. Although the T allele is the most frequent one in this population and its frequency was 86.7% in patients compared with 91.7% in controls [OR=1.705, 95% CI= 0.916-3.172]. Also, the SMAD7 genotypes were not associated with any clinicopathological characteristics in CRC patients [P>0.05]. For the first time, this study results revealed that this SMAD7 polymorphism couldn't be a potential risk factor for CRC or a prognostic biomarker for prediction of clinicopathological features in an Iranian population. A large-scale case-control study is needed to validate our results

role of Kras mutations and MSI status in diagnosis of colorectal cancer

The aim of the current investigation was to examine the profile of Kras mutations accompanied with MSI [microsattelite instability] status in polyps and colorectal carcinoma tissues in an Iranian population. Kras mutations in colorectal cancer cause resistance to anti-Epidermal Growth Factor Receptor [EGFR]. So it can be considered as a true indicator of EGFR pathway activation status. Kras mutations can be detected in approximately 30% to 40% of all patients with colorectal cancer. The most hot spot of the gene is located in exons 2 and 3. In this study we examined exons 2 and 3 Kras gene using polymerase chain reactions and subsequent sequencing of the exons in 95 patients with sporadic colorectal cancer including 48 tumors and 47 polyps. This study was performed using biopsy samples from the patients. We sequenced the Kras gene in a panel of human colorectal tumors and polyps in addition to detecting MSI status using fluorescent technique. We could detect 6 mutations in tumors including 5 mutations in codon 12 and one mutation in codon 13. Moreover, in polyps 2 mutations were determined in codon 13 and one in codon 12. Microsatellite instability assay revealed the presence of 5 and 6 MSI in tumors and polyps, respectively. Among the MSI mononucleotide markers, NR-21 marker demonstrated the most frequency [60%] in the both groups. Our findings showed that probably the profile of mutations in tumors is not entirely compatible with the pattern of mutations in polyps. However, just one of the mutations, Gly12Asp, was similar in both groups