Abdulaziz A Al-Quorain

Novel KRAS Gene Mutations in Sporadic Colorectal Cancer

Introduction In this article, we report 7 novel KRAS gene mutations discovered while retrospectively studying the prevalence and pattern of KRAS mutations in cancerous tissue obtained from 56 Saudi sporadic colorectal cancer patients from the Eastern Province. Methods Genomic DNA was extracted from formalin-fixed, paraffin-embedded cancerous and noncancerous colorectal tissues. Successful and specific PCR products were then bi-directionally sequenced to detect exon 4 mutations while Mutector II Detection Kits were used for identifying mutations in codons 12, 13 and 61. The functional impact of the novel mutations was assessed using bioinformatics tools and molecular modeling. Results KRAS gene mutations were detected in the cancer tissue of 24 cases (42.85%). Of these, 11 had exon 4 mutations (19.64%). They harbored 8 different mutations all of which except two altered the KRAS protein amino acid sequence and all except one were novel as revealed by COSMIC database. The detected novel mutations were found to be somatic. One mutation is predicted to be benign. The remaining mutations are predicted to cause substantial changes in the protein structure. Of these, the Q150X nonsense mutation is the second truncating mutation to be reported in colorectal cancer in the literature. Conclusions Our discovery of novel exon 4 KRAS mutations that are, so far, unique to Saudi colorectal cancer patients may be attributed to environmental factors and/or racial/ethnic variations due to genetic differences. Alternatively, it may be related to paucity of clinical studies on mutations other than those in codons 12, 13, 61 and 146. Further KRAS testing on a large number of patients of various ethnicities, particularly beyond the most common hotspot alleles in exons 2 and 3 is needed to assess the prevalence and explore the exact prognostic and predictive significance of the discovered novel mutations as well as their possible role in colorectal carcinogenesis.

Psuedomyxoma peritonei secondary to adenocarcinoma of the cecum

Pseudomyxoma peritonei is a rare progressive disease. Patients commonly present with a picture of acute appendicitis or with increasing abdominal girth. We present a case of a 71 year old man who presented with right iliac fossa pain, fever and vomiting. His abdominal examination revealed right iliac fossa mass which was confirmed radiologically. Diagnostic laparoscopy showed jelly like material along with a right iliac fossa mass. The aspirate was negative for malignancy initially. Due to persistance and progression of his disease he underwent right hemicolectomy. Histopathological diagnosis showed moderately differentiated adenocarcinoma of the cecum Duke’s C2.

Zika virus: An emerging pathogen

The clinical presentation is usually asymptomatic in the majority of cases. However, when symptoms are present, they are usually mild and can include low-grade fever, arthralgia, rash, and conjunctivitis.[12] Severe clinical manifestations, including microcephaly, have been described in infants and Guillain-Barre syndrome has been reported as a neurological complication.[13,14] Although the Zika virus infection is mild in more than 80% of cases, further multicenter studies are required to improve the management of the infection.

Methicillin-Resistant Staphylococcus Aureus

1. Barber M. Methicillin-resistant staphylococci J Clin Pathol 1961; 14:385. 2. Klevens RM, Morrison MA, Nadle J, et al. Invasive methicillinresistant staphylococcus aureaus infections in the United States. JAMA 2007; 298; 1763. 3. Wisplinghoff H, Bischoff T, Tallent SM, et al. Nosocomial bloodstream infections in US hospitals: Analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 2004; 39:309. 4. Styers D, Sheehan JM, Hogan P, Sahm DF. Laboratory-based surveillance of current microbial resistance patterns and trends among Staphylococcus aureus: 2005 status in the United States. Ann Clin Micobiol Antimicrob 2006; 5:2. 5. Sader HS, Streit JM, Fritche TR, Jones RN. Antimicrobial susceptibility of gram-positive bacteria isolated from European medical centres: Results of the Daptomycin Surveillance Programme (2002-2004). Clin Microbiol Infect 2006; 12:844. 6. Moran GJ, Krishnadasan A, Gorwitz RJ, et al. Methicillin-resistant S. aureus infections among patients in the emergency department. N. Engl J Med 2006; 355:666. 7. Hersh AL, Chambers HF, Maselli JH, Gonzales R. National trends in ambulatory visits and antibiotic prescribing for skin and softtissue infections. Arch Intern Med 2008; 168:1585. 8. El Amin NM, Faidah HS. Methicillin-resistant Staphylococcus aureus in the western region of Saudi Arabia. Ann Saudi Med; 2012; 32:513-6. 9. Iyer PA, Baghalib I, Albaik M, Kumosani T. Nosocomial infections in Saudi Arabia caused by Methicillin-resistant Staphylococcus aureus. Clinical Microbioloy 2014; 3:3.

Infliximab-induced psoriasis in a patient with crohn's disease

Infliximab is a well-known treatment for inflammatory bowel diseases (IBDs) and psoriasis. Paradoxically, there have been numerous reports of new-onset psoriasis following tumor necrosis factor-α antagonist therapy in patients with IBD. Here, we report a case with Crohn′s disease who developed Infliximab-induced plaque-type psoriasis 4 months after initiation of treatment with Infliximab.

Novel KRAS gene mutations in Saudi colorectal cancer patients

&NA; We report 7 novel KRAS gene mutations discovered while retrospectively studying the prevalence and pattern of KRAS mutations in cancerous tissue obtained from 56 Saudi colorectal cancer patients from the Eastern Province. Methods: Genomic DNA was extracted from paraffin-embedded, formalin-fixed cancerous and noncancerous colorectal tissues. A nested PCR approach was implemented. Successful and specific PCR products were then bi-directionally sequenced. The functional impact of the novel mutations on the K-ras protein was assessed using bioinformatics tools and molecular modeling. Results: KRAS gene mutations were detected in the cancer tissue of 24 out of 56 cases studied. Of these, 11 were in exon 4 (19.64%). The 11 cases with exon 4 aberrations harbored 8 different mutations. All of these except two altered the K-ras protein amino acid sequence and all except one were novel as revealed by COSMIC database. The detected novel mutations were found to be somatic. The molecular modeling data fit with the prediction from Polyphen-2 (polymorphism phenotyping v2) and SIFT (sorting intolerant from tolerant tools), as well as conservation data. One mutation is predicted to be benign and modeling also showed little predicted effect on protein structure. The remaining mutations are predicted to cause substantial changes in the protein structure in line with the predicted damaging effect by polyphen-2 software. Of these, the Q150X nonsense mutation is the second truncating mutation to be reported in colorectal cancer in the literature.1 Conclusions: Our discovery of novel exon 4 KRAS mutations that are, so far, unique to Saudi patients from the Eastern Province may be attributed to environmental factors and/or racial/ethnic variations due to genetic differences. Alternatively, it may be related to the paucity of clinical studies on mutations other than those in codons 12, 13, 61 and 146. Further KRAS testing on a large number of patients, particularly beyond the most common hotspot alleles in exons 2 and 3, is needed to assess the prevalence and explore the exact prognostic and predictive significance of the discovered novel mutations as well as their possible role in colorectal carcinogenesis. ReferencePalmirotta R, Savonarola A, Formica V, et al. A novel K-ras mutation in colorectal cancer. A case report and literature review. Anticancer Res 2009; 29: 3369–74.