Latar Belakang: Kanker nasofaring (KNF) merupakan keganasan yang memiliki distribusi geografis dan etnis yang khas, serta sering dikaitkan dengan mutasi genetik dan faktor lingkungan. Pada penelitian ini dilakukan whole genome dan sekuensing metilasi KNF menggunakan teknologi sekuensing Nanopore untuk mengeksplorasi perubahan genetik dan epigenetik yang signifikan secara klinis yang berkontribusi pada karsinogenesis KNF.Metode: Tujuh sampel biopsi KNF dianalisis menggunakan teknologi Nanopore, mencakup ekstraksi DNA, library preparation, dan analisis bioinformatika seperti basecalling, alignment, dan variant calling. Penelitian ini mengevaluasi small nucleotide variants (SNVs), copy number variations (CNVs), structural variants (SVs), short tandem repeat (STR), serta pola metilasi. Data kelangsungan hidup, respons pengobatan, dan karakteristik klinis juga dianalisis.Hasil: Studi ini mengidentifikasi berbagai varian genetik yang diprediksi memberikan dampak fungsional tinggi pada semua sampel. Onkogen potensial juga teridentifikasi di studi ini. Varian struktural ditemukan lebih sering pada sampel S1, dengan banyak kelainan pada gen DNA repair tetapi tidak ditemukan di sample lain, kelainan ini menunjukkan korelasi prognosis klinis yang buruk. Tumour suppressor gene, termasuk PRKCB, ITGB3, EPHA2, dan CDKN2A, juga mengalami hiper metilasi, dan menunjukkan potensi keterlibatan dalam perkembangan KNF.Kesimpulan: Studi ini menemukan mutasi pada gen DNA repair berkaitan dengan prognosis yang buruk pada KNF. Berbagai mutasi pada tumour suppressor gene dan onkogen ditemukan yang berpotensi berkaitan dengan karsinogenesis KNF.

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Background: Nasopharyngeal carcinoma (NPC) is a malignancy with distinct geographical and ethnic distribution, often linked to genetic mutations and environmental factors. The current study focuses on the whole genome and methylation sequencing of NPC using Nanopore sequencing technology to explore clinically significant genetic and epigenetic alterations contributing to NPC carcinogenesis.

Method: Seven NPC biopsy samples were sequenced using Nanopore technology, covering DNA extraction, library preparation, and bioinformatics analysis, including basecalling, alignment, and variant calling. Small nucleotide variants (SNVs), copy number variations (CNVs), structural variants (SVs), short tandem repeats (STRs), and methylation patterns were assessed using bioinformatic tools. Additionally, survival data, treatment response, and clinical characteristics were analyzed.

Results: The study identified various high-impact genetic variants across all samples. Potential oncogenes were also identified. Structural variants were notably more frequent in sample S1, with aberrant multiple DNA repair genes, not found in other samples, which correlated with poor clinical prognosis. Tumour suppressor genes including PRKCB, ITGB3, EPHA2, and CDKN2A were also frequently hypermethylated in our NPC.

Conclusion: This study found aberrant DNA repair genes to be associated with poor prognosis in NPC. Furthermore, various mutation in tumour suppressor genes and oncogenes were identified which were potential driver carcinogenesis in NPC.