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Based on the analysis of patients with Peutz-Jeghers syndrome (PJS), Serine threonine kinase11 (STK11) is known as a tumor suppressor gene, which is involved in cell polarization, regulation of apoptosis, and DNA damage response. In this case report study, we examined STK11 gene sequencing in a 42-year-old woman with mucocuta neous pigmentation and positive family history. Endoscopy and colonoscopy showed >1000 polyps throughout the stomach/colon (PJ-type hamartomas). The larger polyp in the stomach was resected and the small bowel imaging detected multiple jejunum/ileum small polyps. The data released from the sequencing results revealed five alterations in exons 1 to 5. The major mutation in stop codon was reported as converted to the amino acid tryptophan (TRP) to tyrosine (TER). The TGG codon was converted to TAG by mutation. Finally, another novel mutation in STK11 stop codon as a 'de novo' variant was seen. It is predicted that stop codon mutations make the affected person susceptible to developing colorectal cancer. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to evaluate the distribution of PIK3CA E545K mutation in Iranian CRC patients and explored its roles in disease prognosis. Background: Deregulation of the phosphoinositide 3-kinase (PI3K) pathway contributes to the progression of tumors. The p110a (PIK3CA), a catalytic subunit of PIK3, is mutated in many types of cancers. Exon 9 (E545K) is the most frequently mutated hotspot in PIK3CA in colorectal cancer (CRC). However, the prognostic role of PIK3CA E545K mutation needs to be elucidated. Methods: Tumors from 187 CRC patients were retrospectively collected from the Taleghani and Shohada Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran, between 2010 and 2017. PIK3CA E545K status was detected in Formalin-fixed paraffin-embedded (FFPE) tissues using PCR-RFLP methods, and validated by pyrosequencing. Correlations between PIK3CA E545K mutation clinicopathological features were analyzed. Results: The frequency of PIK3CA E545K gene mutations in CRC patients was 10.7%. Significant correlations were observed in PIK3CA E545K mutation with tumor differentiation and TNM stage (p < 0.042 and p = 0.033, respectively). Kaplan-Meier analysis showed a worse prognosis in overall survival (OS) in patients with PIK3CA E545K mutation (p < 0.001). Multivariate analysis indicated that PIK3CA E545K mutation was a detrimental factor for OS (HR = 6.497, 95% CI: 2.859-14.768, p < 0.021). Conclusion: A high frequency of PIK3CA E545K mutation was detected in Iranian CRC patients. The results of the present study suggested that PIK3CA E545K mutation may be associated with poor prognosis. These findings require further confirmation via prospective studies with larger samples. [ABSTRACT FROM AUTHOR]

The human epidermal growth factor 2 (HER2) gene undergoes various mutations that could alter its activity or respond to the antibody therapies. Cetuximab, a known anti‐EGFR monoclonal antibody (mAB), is widely administered in metastatic colorectal cancer (mCRC) cases. Here we identified mCRC patients who did not respond to cetuximab (500 mg/m2, q2w) after fluoropyrimidine/oxaliplatin regimen failure. Tumor samples were examined with immunohistochemistry for protein distribution, polymerase chain reaction (PCR) sequencing for mutation detection and real‐time PCR for mRNA expression pattern analysis between cetuximab sensitive and resistance patients. The conformational differences of normal and mutated protein structures were predicted by bioinformatics analysis. The 5‐year survival rates of target groups were estimated using the Kaplan–Meier method. Immunohistochemistry showed that all cases had high level of HER2 protein. No K‐Ras or B‐Raf mutation was observed among the study population; however, cetuximab resistance patients harbored a somatic mutation R784G at the exon 20 region of HER2 coding sequence. According to bioinformatics analysis, this mutation caused a notable misfold in protein conformation. Meanwhile, survival analysis showed R784G mutated mCRC patients had shortened survival rate compared with the mCRC cases with wild‐type HER2. Collectively, these data report a new mechanism of resistance to cetuximab and might be applicable in modifying new therapeutic strategies for HER2 involved cancers. [ABSTRACT FROM AUTHOR]

Aim: We aimed to explore the frequency of BRAFV600E 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 BRAFV600E mutation with malignant transformation and clinical outcome of different tumors, including CRC. These findings suggest that BRAFV600E 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. BRAFV600E 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 BRAFV600E 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. [ABSTRACT FROM AUTHOR]

Aim: 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. Background: 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. Patients and methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]