An Initial Indonesian Genome-Wide SNP-Array Study with Functional Variant Prioritization Reveals NASP and GPR78...

Area of Science:

• Genomics
• Oncology
• Bioinformatics

Background:

• Understanding hepatocellular carcinoma (HCC) biology requires population-specific genomic data, especially from underrepresented regions.
• Genomic profiling of Indonesian HCC patients is crucial for identifying unique genetic drivers.
• Previous studies have not extensively covered the Indonesian population for HCC genomic variations.

Purpose of the Study:

• To conduct exploratory single-nucleotide polymorphism (SNP)-array profiling of HCC tumors from Indonesian patients.
• To prioritize candidate functional variants using a systematic in silico framework.
• To identify novel genetic targets for hepatocellular carcinoma in a specific demographic.

Main Methods:

• Retrospective analysis of 15 formalin-fixed paraffin-embedded (FFPE) HCC tumor samples.
• Genome-wide SNP genotyping using the Illumina Asian Screening Array.
• In silico functional prioritization of variants using Ensembl Variant Effect Predictor and gene-level burden analysis.

Main Results:

• 11 samples and 104 prioritized variants were identified after quality control and filtering.
• Predominant variant types included splice-region, missense, and regulatory changes.
• Nuclear Autoantigenic Sperm Protein (NASP) and G protein-coupled receptor 78 (GPR78) emerged as top candidate genes.

Conclusions:

• This exploratory study offers a hypothesis-generating framework for variant prioritization in Indonesian HCC.
• NASP and GPR78 are preliminary candidate genes requiring further validation.
• Larger cohorts with matched normal tissue and sequencing are needed for confirmation.