Sains Malaysiana 47(12)(2018): 3095–3105

http://dx.doi.org/10.17576/jsm-2018-4712-20

 

Prediction of Colorectal Cancer Driver Genes from Patients' Genome Data

(Penentuan Gen Pemandu Kanser Kolorektum daripada Data Genomik Pesakit)

 

MUHAMMAD-IQMAL ABDULLAH & NOR AZLAN NOR MUHAMMAD*

 

Centre for Bioinformatics Research, Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor Darul Ehsan, Malaysia

 

Diserahkan: 14 September 2018 /Diterima: 14 September 2018

 

ABSTRACT

Colorectal cancer refers to the cancer that occurs in the colon and rectum. It has been established as the third most common cancer and the forth one in causing worldwide mortality. Cancer caused by the mutation of several genes that usually involved in the regulation of cell proliferation, growth and cell death. The mutation that leads to abnormal function of genes, either in enabling the genes to gain or loss of function was termed as driver mutation and the genes with driver mutation ability was termed as driver genes. The identification of driver genes provides insight on mechanistic process of cancer development where this information can be used to further understand their mode of action for causing dysregulation in signaling pathways. In this study, two bioinformatic tools, i.e. CGI and iCAGES were used to predict potential driver genes from the genome of eight colorectal cancer patients with annotated variants datasets. 44 unique driver genes and 21 pathways have been identified; such as p53 signaling, PI3K-AKT, Endocrine resistance, MAPK and cell cycle pathways. The identification of these pathways can lead to the identification of potential drugs targeting these pathways.

 

Keywords: Cancer driver genes; colorectal cancer; pathway analysis; precision medicine

 

ABSTRAK

Kanser kolorektum adalah kanser yang berlaku pada kolon dan juga rektum. Ia merupakan kanser ketiga yang paling kerap dilaporkan serta yang keempat menjadi punca kematian tertinggi di seluruh dunia. Kanser berlaku disebabkan oleh mutasi daripada gen tertentu yang terlibat di dalam pengawalaturan proliferasi, pertumbuhan dan kematian sel. Mutasi yang mencetuskan perubahan pada fungsi gen sama ada meningkatkan atau menghilangkan fungsinya dikenali sebagai mutasi pemandu, manakala gen yang mempunyai mutasi pemandu dikenali sebagai gen pemandu kanser. Pengenalpastian gen pemandu membolehkan mekanisme pembentukan kanser dapat dikenal pasti melalui peranannya dalam pengawalaturan tapak jalan. Dalam kajian ini, dua perisian bioinformatik iaitu CGI dan iCAGES telah digunakan untuk mengenal pasti calon gen pemandu daripada set data varian yang telah dianotasi daripada genom lapan pesakit kanser kolorektum. Sebanyak 44 gen pemandu dan 21 tapak jalan terlibat telah dikenal pasti; antaranya adalah tapak jalan pengisyaratan p53, PI3K-AKT, rintangan endokrin dan MAPK. Kesemua tapak jalan ini berpotensi untuk dijadikan sasaran terapi.

 

Kata kunci: Analisis tapak jalan; gen pemandu kanser; kanser kolorektum; perubatan jitu

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*Pengarang untuk surat menyurat; email: norazlannm@ukm.edu.my