• Sobia Hassan Pathology Department, Ziauddin University, Karachi-Pakistan
  • Ambrina Khatoon Research Department, Ziauddin University, Karachi-Pakistan
  • Uzma Bukhari Dow University of Health Sciences, Karachi-Pakistan
  • Talat Mirza Pathology Department, Ziauddin University, Karachi-Pakistan



Genetic mutations, Biological Pathways, insilico, BRAF, KRAS


Background: Identification of gene targets and biological pathways involved in colorectal carcinoma (CRC) is essential for better management of patients. Our study aims to highlight common somatic mutations in colorectal carcinoma and to identify dysregulated pathways and gene enrichment based on KRAS and BRAF interaction network analysis. Methods: By using cancer browser tool in COSMIC database, mutation frequencies of the top 20 mutated genes listed for colorectal adenocarcinoma were identified. The most frequent variants of   selected genes were explored with ClinVar database which led to identification of protein change along with its cytogenic location, variant type, variant length and the associated single nucleotide polymorphism (SNP). These identified SNPs were searched in Pakistani database using 1000genome in an attempt to identify common polymorphisms. Using the database the number of clinical trials based upon these selected mutations was explored. Enrichment and protein interaction (PI) analysis of KRAS and BRAF was carried out to reveal significant biological pathways associated with these genes. Results: In cumulative data, among all variants about 57% of substitution mutations are observed to be G>A including mutations in KRAS, Tp53, SMAD4, PI3K and NRAS. The mutations of KRAS (c.35G>A), TP53 (c.524G>A) and APC (c.4348C>T) were found to be pathogenic with single nucleotide variation and variant length of 1bp. Searching 1000genome database revealed that  100 % of alleles found in East Asian population  studied  are ‘C’(frequency=1). Significant biological pathways (<0.05) identified by our search include Trk receptor signalling mediated by the MAPK pathway, signalling to p38 via RIT and RIN, signalling to ERKs, Frs2-mediated activation, ARMS-mediated activation and prolonged ERK activation events. Conclusion: Our study highlights the role of genetic profiling in CRC, with emphasis on mutations which may define treatment outcome. Targeting several collateral pathways simultaneously may be further explored to improve colorectal cancer therapeutics.

Author Biographies

Sobia Hassan, Pathology Department, Ziauddin University, Karachi-Pakistan

Pathology Department PhD Scholar

Ambrina Khatoon, Research Department, Ziauddin University, Karachi-Pakistan

Assistant Professor Research Department,  

Uzma Bukhari, Dow University of Health Sciences, Karachi-Pakistan

Professor & HOD pathology DIMC Section Head & consultant histopathologist DOw Labs (DDRRL)    

Talat Mirza, Pathology Department, Ziauddin University, Karachi-Pakistan

Meritorious Professor of Pathology Executive Director research FHS Ziuddin University


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