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Breakthrough in the Genetic Understanding of Oral Cancer

 

Breakthrough in the Genetic Understanding of Oral Cancer

 

      Taiwan – Are people of certain races more susceptible to particular malignancies? Despite the notion that cancer is a multifactorial disease, genetic predisposition has long been a sought-after question for oncologists and biologist. A research team at Chang Gung University, led by Prof. Yu-Sun Chang and head and neck surgeon Dr. Kai-Ping Chang, addressed this burning issue in a study recently published in the journal Nature Communications.

 

      The research team focused on a type of cancer called oral squamous cell carcinoma (OSCC), which is a worldwide malignancy with high prevalence in Taiwan and Asia. In search of genome-encoded marker that could help diagnose and discriminate tumor, the team employed a “cross-omics” workflow that integrated experimental data garnered from multiple platforms – high-throughput DNA and RNA sequencing as well as proteome profiling. They then studied 50 pairs of Taiwanese OSCC patient specimens of tumor and adjacent normal tissues.

 

      In this regional patient cohort, the team made the critical discovery of a predominant mutation signature associated with cytidinedeaminase APOBEC, an enzyme family previously implicated in anti-viral and innate immunity. This unique sequence profile in tumor cells is likely attributed to a frequent deletion polymorphism in the cytidinedeaminases gene cluster APOBEC3 resulting inincreased expression of APOBEC3A.

      Prof. Chang pointed out that, while this APOBEC-deletion germline polymorphism is also detected in the US-led TCGA tumor database, only ~6% of the patient samples exhibit this as compared to ~50% of the Taiwanese group. Clinical analysis also revealed that this genetic factor could be of prognostic use. Finally, using similar genomic approach, theirfinding could be extended to and recapitulated in other cancer types.This interesting work is supported by Chang Gung Memorial Hospital, Ministry of Education, and Ministry of Science and Technology of Taiwan.

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