Molecular biologic, immunogenetic, and Epstein-Barr virus studies on nasal NK/T-cell lymphoma

分析32例鼻腔NK/ t细胞淋巴瘤患者肿瘤抑制基因p53、b-catenine基因和ras基因的突变、p53蛋白和b-catenine的表达及临床预后。32例患者中，检测到p53基因6个突变（2个沉默，4个错义），b-catenine基因5个突变（3个沉默，2个错义），N-和K-ras基因各1个突变。p53腮腺蛋白过表达15例，b-连环蛋白过表达4例。这些基因突变的患者预后较差。多因素分析显示p53基因突变是最独立的致病因素。应用pcr扩增产物对7例鼻NK/ t细胞淋巴瘤患者的Epstein-Barr病毒基因LMP-1总区和LMP-2A外显子6进行直接序列分析。在所有7个样本中均检测到LMP-1基因3' c端30 bp的缺失。在LMP-1基因中，7例患者均检测到43个相似的核苷酸变化，7例患者中发现11个序列变异。对于LMP-2A基因外显子6的序列，7例患者在密码子348处发现了相似的核苷酸变化（AGC变为ACC，丝氨酸变为苏氨酸）。

Mutations of p53 tumor suppressor gene, b-catenine gene, and ras gene, expressions of p53 protein and b-catenine, and clinical outcome were analyzed in 32 patients with nasal NK/T-Cell lymphoma. Of 32 patients, 6 mutations (2 silent and 4 missense) of p53 gene, 5 mutations (3 silent and 2 missense) of b-catenine gene, and each 1 mutation of N- and K-ras gene were detected. Overexpression of p53 parotein and b-catenine protein were found in 15 and 4 patients, respectively. The patients with mutations of these genes showed poor prognosis. Multivariate analysis revealed p53 gene muation as a most independent pronostic factor.Direct sequence analyzes for total region of LMP-1 and the exon 6 of LMP-2A in Epstein-Barr vius gene were performed using PCR-amplified products in 7 patients with nasal NK/T-cell lymphoma. A 30-bp deletion in the 3' C-terminal region of the LMP-1 gene was detected in all 7 samples. In the LMP-1 genes, 43 similar nucleotide changes were detected in all 7 patients and 11 sequence variations were found among 7 patients. With regard to the sequence of in exon 6 of LMP-2A gene, a similar nucleotide change (AGC to ACC, serine to threonine) at codon 348 was determined in all 7 patients.