Epstein-Barr virus latent membrane protein-1 (LMP-1) 30-bp deletion and Xho I-loss is associated with type III nasopharyngeal carcinoma in Malaysia.

Epstein-Barr virus latent membrane protein-1 (LMP-1) 30-bp deletion and Xho I-loss is associated with type III nasopharyngeal carcinoma in Malaysia.
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DOI:
10.1186/1477-7819-6-18
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发表时间:
2008-02-15
影响因子:
3.2
通讯作者:
Seow HF
Seow HF
中科院分区:
医学3区
文献类型:
--
作者:
See HS;Yap YY;Yip WK;Seow HF

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鼻咽癌(NPC)是一种人类上皮肿瘤,在中国南方和东南亚的中国人中发病率很高,与EB病毒(EB病毒)有关。病毒基因组中含有一个致癌基因,即潜伏膜蛋白1(LMP 1)基因,已知的变异体如30-bp的缺失和XhoI限制性位点的缺失已被发现,但这些变异体与人群特征和组织学类型的关系尚不清楚。本研究应用聚合酶链反应(PCR)技术检测了42例鼻咽癌组织、10例非恶性组织石蜡包埋标本及35例鼻咽癌患者血浆中EB病毒LMP 1基因变异。采用SPSS软件进行统计学分析。LMP 130-bp缺失在鼻咽癌组织中检出率为55.9%(19/34),在血浆中检出率为24.1%(7/29),而在非恶性肿瘤组织中缺失率为8.0%(8/8)。仅5/29例(17.2%)血浆标本中存在30 bp缺失和非缺失的变异体,而鼻咽癌组织中未发现。LMP 1基因XhoI酶切位点缺失率分别为87.2%(34/39)和36.7%(11/30)。非恶性鼻咽组织(8/8)均未携带XhoI缺失变体。在16/18名中国人和3/15名马来人以及13/16名III型(未分化癌)和1/6名I型(角化鳞状细胞癌)中检测到LMP 1 30-bp缺失。在19/19名中国人和14/19名马来人中发现了XhoI缺失,在18/18名III型(未分化)和2/5名I型(角化鳞状细胞癌)中发现了XhoI缺失。统计学分析显示,这些变异与种族(30-bp缺失,p < 0.05; XhoI缺失,p = 0.046)和NPC组织学类型(30-bp缺失,p = 0.011; XhoI缺失,p = 0.006)相关。32例鼻咽癌组织中19例(59.4%)和24例血浆标本中6例(25%)同时存在30 bp缺失和XhoI酶切位点缺失。与中国人种有显著相关性,而与组织学类型无关。LMP 1 30-bp缺失的发生率为56%,低于先前报道的NPC组织中75-100%的发生率。仅在5/29份血浆样品中发现了具有和不具有30-bp缺失的变体的共存。鼻咽癌中XhoI限制性位点丢失的发生率与来自中国南方等流行地区的其他研究相当。首次发现LMP 1 30-bp缺失或XhoI缺失与中国人和III型NPC相关。在非恶性组织中未发现这两种变体。这些变异对中国人和III型NPC疾病进展和结局的影响需要进一步研究。
Nasopharyngeal carcinoma (NPC) is a human epithelial tumour with high prevalence amongst Chinese in Southern China and South East Asia and is associated with the Epstein-Barr virus (EBV). The viral genome harbours an oncogene, namely, the latent membrane protein 1 (LMP1) gene and known variants such as the 30-bp deletion and loss of XhoI restriction site have been found. Less is known about the relationship between these variants and the population characteristics and histological type. In this study, the EBV LMP1 gene variants from 42 NPC and 10 non-malignant archived formalin fixed, paraffin-embedded tissues, as well as plasma from another 35 patients with nasopharyngeal carcinoma were determined by using Polymerase Chain Reaction (PCR). Statistical analysis was performed by using SPSS programme. LMP1 30-bp deletion was detected in 19/34 (55.9%) of NPC tissues, 7/29 (24.1%) of plasma but absent in non-malignant tissues (8/8). Coexistence of variants with and without 30bp deletion was found only in 5/29 (17.2%) plasma samples but not in NPC tissues. The loss of XhoI restriction site in LMP1 gene was found in 34/39 (87.2%) of the NPC tissues and 11/30 (36.7%) of plasma samples. None of the non-malignant nasopharyngeal tissues (8/8) harbour XhoI-loss variants. LMP1 30-bp deletion was detected in 16/18 Chinese versus 3/15 Malays and 13/16 type III (undifferentiated carcinoma) versus 1/6 type I (keratinizing squamous cell carcinoma). XhoI-loss was found in 19/19 Chinese versus 14/19 Malays and 18/18 type III (undifferentiated) versus 2/5 type I (keratinizing squamous cell carcinoma). Statistical analysis showed that these variants were associated with ethnic race (30-bp deletion, p < 0.05; XhoI-loss, p = 0.046) and histological type of NPC (30-bp deletion, p = 0.011; XhoI-loss, p = 0.006). Nineteen out of 32 NPC tissues (19/32; 59.4%) and 6/24 (25%) of plasma samples showed the coexistence of both the 30-bp deletion and the loss of XhoI restriction site. A significant relationship was found with the Chinese race but not histological type. The incidence rate of 56% for LMP1 30-bp deletion was lower compared to previously reported rates of 75–100% in NPC tissues. Coexistence of variants with and without 30-bp deletion was found only in 5/29 plasma samples. The incidence rate of XhoI restriction site loss in NPC was comparable to other studies from endemic regions such as Southern China. For the first time, the presence of LMP1 30-bp deletion or XhoI-loss was associated with the Chinese race and type III NPC. Both these variants were not found in non-malignant tissues. The influence of these variants on disease progression and outcome in Chinese and type III NPC requires further investigation.
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