Adham Marlinda, Rachmadi Lisnawati, Wibowo Heri, Gondhowiardjo Soehartati A
Department of Radiation Oncology, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia.
Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Immunotargets Ther. 2024 Mar 18;13:173-182. doi: 10.2147/ITT.S452117. eCollection 2024.
Nasopharyngeal cancer (NPC) is a complex cancer due to its unique genomic features and association with the Epstein-Barr virus (EBV). Despite therapeutic advancements, NPC prognosis remains poor, necessitating a deeper understanding of its genomics. Here, we present a comprehensive whole genome sequencing (WGS) view of NPC genomics and its correlation with the phenotype.
This study involved WGS of a clinical NPC biopsy specimen. Sequencing was carried out using a long read sequencer from Oxford Nanopore. Analysis of the variants involved correlation with the phenotype of NPC.
A loss of genes within chromosome 6 from copy number variation (CNV) was found. The lost genes included HLA-A, HLA-B, and HLA-C, which work in the antigen presentation process. This loss of the major histocompatibility complex (MHC) apparatus resulted in the tumour's ability to evade immune recognition. The tumour exhibited an immunologically "cold" phenotype, with mild tumour-infiltrating lymphocytes, supporting the possible etiology of loss of antigen presentation capability. Furthermore, the driver mutation PIK3CA gene was identified along with various other gene variants affecting numerous signaling pathways.
Comprehensive WGS was able to detect various mutations and genomic losses, which could explain tumour progression and immune evasion ability. Furthermore, the study identified the loss of other genes related to cancer and immune pathways, emphasizing the complexity of NPC genomics. In conclusion, this study underscores the significance of MHC class I gene loss and its probable correlation with the cold tumour phenotype observed in NPC.
鼻咽癌（NPC）因其独特的基因组特征以及与爱泼斯坦-巴尔病毒（EBV）的关联而成为一种复杂的癌症。尽管治疗取得了进展，但鼻咽癌的预后仍然很差，这就需要对其基因组学有更深入的了解。在此，我们展示了鼻咽癌基因组学的全面全基因组测序（WGS）视图及其与表型的相关性。
本研究对一份临床鼻咽癌活检标本进行了全基因组测序。使用牛津纳米孔的长读长测序仪进行测序。对变异的分析涉及与鼻咽癌表型的相关性。
发现拷贝数变异（CNV）导致6号染色体上的基因缺失。缺失的基因包括在抗原呈递过程中起作用的HLA-A、HLA-B和HLA-C。主要组织相容性复合体（MHC）装置的这种缺失导致肿瘤逃避免疫识别的能力。肿瘤表现出免疫“冷”表型，肿瘤浸润淋巴细胞较少，支持了抗原呈递能力丧失的可能病因。此外，还鉴定出驱动突变PIK3CA基因以及影响众多信号通路的各种其他基因变异。
全面的全基因组测序能够检测到各种突变和基因组缺失，这可以解释肿瘤进展和免疫逃避能力。此外，该研究还确定了与癌症和免疫通路相关的其他基因的缺失，强调了鼻咽癌基因组学的复杂性。总之，本研究强调了MHC I类基因缺失的重要性及其与鼻咽癌中观察到的冷肿瘤表型的可能相关性。
