PLoS One：中国广州EBV相关胃癌LMP2A序列变化研究

潜伏膜蛋白2A (LMP2A)，表达于大多数人类疱疹病毒(EBV)有关的恶性肿瘤，已经被证明是潜伏性感染及上皮细胞转化的主要诱因。

除此以外，它也可以作为基于CTL（cytotoxic T lymphocyte，细胞毒性T淋巴细胞）治疗EBV关联的恶性肿瘤的靶点。中国南部广州有鼻咽癌(NPC)地方性发病区，在目前的研究中，中山大学的邵春奎教授研究了该地区EBV相关的胃癌(EBVaGC)以及健康EBV携带者的LMP2A的序列变化。

广泛的序列变化发现于LMP2A基因，但是没有与B95.8原型一致的序列，并且在所有的隔离群里没有发现一致突变。在LMP2A氨基末端，免疫受体酪氨酸活化基序(ITAM)以及PY模体是严格保守的，这表明，它们对病毒感染起着重要的作用。

研究发现，在LMP2A跨膜区域中的17个CTL抗原表位，有8个表位可以通过至少一个点突变受影响。研究人员表示，这可能暗示着在实施LMP2A定向免疫治疗时应该考虑LMP2A多态性的作用。

残胃癌(GRC)EBVaGC的LMP2A的多态性研究在世界上属于首次研究，研究发现，残胃癌 (GRC)EBVaGC中LMP2A的序列变化有些不同于常规胃癌。

EBVaGC的LMP2A的序列变化类似于有咽喉疾病的健康的EBV携带者，表明这些变化起因于地理有关的多态性，而不是因为EBVaGC关联的突变。

这是第一次详细研究了EBVaGC中LMP2A的多态性。相关文章发表在3月28日的PLoS One。（生物谷Deepblue编译）

doi: 10.1371/journal.pone.0034276
PMC:
PMID:

Sequence Variations of Latent Membrane Protein 2A in Epstein-Barr Virus-Associated Gastric Carcinomas from Guangzhou, Southern China

Jing Han, Jian-ning Chen, Zhi-gang Zhang, Hai-gang Li, Yun-gang Ding, Hong Du, Chun-kui Shao.

Latent membrane protein 2A (LMP2A), expressed in most Epstein-Barr virus (EBV)-associated malignancies, has been demonstrated to be responsible for the maintenance of latent infection and epithelial cell transformation.Besides, it could also act as the target for a CTL-based therapy for EBV-associated malignancies. In the present study, sequence variations of LMP2A in EBV-associated gastric carcinoma (EBVaGC) and healthy EBV carriers from Guangzhou, southern China, where nasopharyngeal carcinoma (NPC) is endemic, were investigated.Widespread sequence variations in the LMP2A gene were found, with no sequence identical to the B95.8 prototype. No consistent mutation was detected in all isolates. The immunoreceptor tyrosine-based activation motif (ITAM) and PY motifs in the amino terminus of LMP2A were strictly conserved, suggesting their important roles in virus infection;while 8 of the 17 identified CTL epitopes in the transmembrane region of LMP2A were affected by at least one point mutation, which may implicate that the effect of LMP2A polymorphisms should be considered when LMP2A-targeted immunotherapy is conducted.The polymorphisms of LMP2A in EBVaGC in gastric remnant carcinoma (GRC) were for the first time investigated in the world. The LMP2A sequence variations in EBVaGC in GRC were somewhat different from those in EBVaGC in conventional gastric carcinoma.The sequence variations of LMP2A in EBVaGC were similar to those in throat washing of healthy EBV carriers, indicating that these variations are due to geographic-associated polymorphisms rather than EBVaGC-associated mutations.This, to our best knowledge, is the first detailed investigation of LMP2A polymorphisms in EBVaGC in Guangzhou, southern China, where NPC is endemic.