Mutations of the β2-microglobulin gene result in a lack of HLA class I molecules on melanoma cells of two patients immunized with MAGE peptides
Mutations of the β2-microglobulin gene result in a lack of HLA class I molecules on melanoma cells of two patients immunized with MAGE peptides
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DOI：
10.1111/j.1399-0039.1998.tb03082.x
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发表时间：
1998-12-01
期刊：
影响因子：
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通讯作者：
Garrido, F
中科院分区：
文献类型：
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作者：
Benitez, R;Godelaine, D;Garrido, F
在两个接受MAGE肽免疫的转移性黑色素瘤患者的肿瘤细胞中发现了β(2)-微球蛋白基因突变，一个突变消除了开始密码子，而另一个突变引入了过早停止密码子，根据序列数据和微卫星杂合性的丧失，两个肿瘤的第二个β(2)-微球蛋白等位基因似乎都丢失了。缺乏β(2)-微球蛋白基因产物导致肿瘤细胞表面缺乏HLA I类抗原。这可能解释了为什么两例患者的肿瘤在免疫治疗后仍进展，并表明了深入分析肿瘤细胞抗原递呈能力的必要性，以解释涉及抗肿瘤疫苗接种的临床试验。
Mutations have been identified in the beta(2)-microglobulin gene of tumor cells of two metastatic melanoma patients who received immunizations with MAGE peptides, One mutation abolishes the start codon whereas the other introduces a premature stop codon, The second beta(2)-microglobulin allele of both tumors appears to be lost on the basis of sequence data and loss of microsatellite heterozygosity. The lack of beta(2)-microglobulin gene product results in the absence of HLA class I antigens on the surface of the tumor cells. This may explain why the tumors of both patients progressed despite the immunization treatment and shows the necessity of analyzing in depth the antigen presentation capability of the tumor cells for the interpretation of clinical trials involving anti-tumor vaccination.