PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
■鼻咽癌（NPC）是一种复杂的癌症，由于其独特的基因组特征以及与EB病毒（EBV）的关联。尽管治疗进展，NPC预后仍然很差，需要对其基因组学有更深入的了解。这里,我们提出了全面的NPC基因组学全基因组测序（WGS）观点及其与表型的相关性。
■本研究涉及临床NPC活检标本的WGS。使用来自牛津纳米孔的长读数测序仪进行测序。变异分析涉及与NPC表型的相关性。
■发现6号染色体内的基因因拷贝数变异（CNV）而丢失。丢失的基因包括HLA-A,HLA-B,和HLA-C,在抗原呈递过程中起作用。主要组织相容性复合物（MHC）装置的这种丧失导致肿瘤逃避免疫识别的能力。肿瘤表现出免疫学上的“冷”表型，有轻微的肿瘤浸润淋巴细胞，支持抗原呈递能力丧失的可能病因。此外，已鉴定出驱动突变PIK3CA基因以及影响众多信号通路的各种其他基因变体.
■全面的WGS能够检测到各种突变和基因组丢失，这可以解释肿瘤进展和免疫逃避能力。此外，该研究发现了与癌症和免疫途径相关的其他基因的丢失，强调NPC基因组学的复杂性。总之,这项研究强调了MHCI类基因丢失的重要性及其与NPC中观察到的冷肿瘤表型的可能相关性。
■本研究涉及临床NPC活检标本的WGS。使用来自牛津纳米孔的长读数测序仪进行测序。变异分析涉及与NPC表型的相关性。
■发现6号染色体内的基因因拷贝数变异（CNV）而丢失。丢失的基因包括HLA-A,HLA-B,和HLA-C,在抗原呈递过程中起作用。主要组织相容性复合物（MHC）装置的这种丧失导致肿瘤逃避免疫识别的能力。肿瘤表现出免疫学上的“冷”表型，有轻微的肿瘤浸润淋巴细胞，支持抗原呈递能力丧失的可能病因。此外，已鉴定出驱动突变PIK3CA基因以及影响众多信号通路的各种其他基因变体.
■全面的WGS能够检测到各种突变和基因组丢失，这可以解释肿瘤进展和免疫逃避能力。此外，该研究发现了与癌症和免疫途径相关的其他基因的丢失，强调NPC基因组学的复杂性。总之,这项研究强调了MHCI类基因丢失的重要性及其与NPC中观察到的冷肿瘤表型的可能相关性。
