Novel KRAS Gene Mutations in Sporadic Colorectal Cancer

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.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.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.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

Adult desmoplastic medulloblastoma

Medulloblastoma is more common in young age and rare in adult age. Some characteristics that characterize medulloblastoma in adults compared with children: Lateral cerebellar location, heterogeneous signal intensity on magnetic resonance imaging, desmoplastic histological variant and more favorable prognosis. Preoperative diagnosis is important for correct management of these patients. However, because of the low incidence of medulloblastoma in adults, preoperative diagnosis still challenging and prognostic factors and best treatment options are still controversial. We report a case of a 31-year-old male patient who presented with a rare case of posterior fossa medulloblastoma

A case of trigeminal schwannoma presenting as a parasellar mass

Schwannoma's of considerable size arising from the trigeminal nerve are very rare. Here, a case of a large right-sided parasellar mass diagnosed as a trigeminal schwannoma is reported. Complete resection of the tumor was successfully achieved. The patient had an excellent postoperative course

Clinical, pathological and immunohistochemical findings in colorectal cancer cases with novel K-ras mutations compared to cases with other K-ras mutations.

<p>Clinical, pathological and immunohistochemical findings in colorectal cancer cases with novel K-ras mutations compared to cases with other K-ras mutations.</p

Molecular modeling data of KRAS exon 4 non-synonymous mutations.

<p>Molecular modeling data of KRAS exon 4 non-synonymous mutations.</p

Mutations detected in exon 4. Exon 4 of all samples was sequenced as described in text.

<p>Fifty six colorectal cancer tissue samples were analyzed. Only those with a mutation in exon 4 are illustrated in the table. All detected mutations were confirmed via sequencing the opposite strand. HGVS guidelines for mutation nomenclature were followed.</p><p>Mutations detected in exon 4. Exon 4 of all samples was sequenced as described in text.</p

Primers used for KRAS exon 4 mutation analysis.

<p>Primers used for KRAS exon 4 mutation analysis.</p

Images of Sanger sequencing electropherogram showing novel mutations (left panel) detected in the study cohort (reverse direction) and the corresponding wild type sequence (right panel) of normal tissue sections for the same patient indicating the somatic origin of detected exon 4 mutations.

<p>All illustrated mutations were confirmed via sequencing the forward strand. Sample number and mutation nomenclature according to HGVS guidelines are highlighted above each mutation. Arrows point to the location of base pair change.</p

Clinical pathological and immunohistochemical findings in colorectal cancer cases with novel KRAS mutations.

<p>Clinical pathological and immunohistochemical findings in colorectal cancer cases with novel KRAS mutations.</p