The roles of HLA genes relevant to gene therapy for human melanoma.

目前尚不清楚在日本，人类白细胞抗原是否与恶性黑色素瘤有关。肢端雀斑黑色素瘤(ALM)可能发生在日本人，但在高加索人中并不常见。为了阐明人类白细胞抗原基因与黑色素瘤发生发展的关系，我们用58例日本无关黑色素瘤患者(结节性黑色素瘤20例，ALM 20例，浅表性播散性黑色素瘤9例，恶性雀斑4例，膜源性黑色素瘤4例，转移性黑色素瘤1例)的外周血淋巴细胞进行了人类白细胞抗原的群体调查。结果表明，黑色素瘤与人类白细胞抗原B13(P&lt；0.0001)和CW6(P&lt；0.03)有很强的相关性。NM组中，HLAB13基因频率极高。ALM患者的HLA-B51基因频率明显升高(9/20=45(%)vs15/120=13(%))。而在神经母细胞瘤中，其出现频率极低(1/20=5(%))。在所有的黑色素瘤中，HL-B61表达降低。因此，人类白细胞抗原连锁免疫反应或免疫抑制基因(S)似乎与人类黑色素瘤的易感性有关。NM和ALM之间可能存在遗传差异。

It has not been clear whether HLA antigens are associated with malignant melanoma in Japan. Acral lentiginous melanoma (ALM) may occur in Japanese but is uncommon in Caucasians. In order to elucidate involvement of HLA genes relevant to development of melanoma, we performed an HLA population survey, by using peripheral blood lymphocytes obtained from 58 unrelated Japanese patients with melanoma (20 nodular melanoma (NM) , 20 ALM,9 superficial spreading melanoma, 4 lentigo maligna melanoma, 4 melanoma derived from the membrane and 1 metastatic melanoma) . The results showed that there was a strong association between melanoma and HLA-B13 (p<0.0001) and Cw6 (p<0.03) . In NM,the frequency of HLA-B13 was extremely high. An increased frequency of HLA-B51 was seen in ALM (9/20=45 (%) vs 15/120=13 (%) in normal control) . In contrast, its frequency in NM was extremely decreased (1/20=5 (%) ) . HLA-B61 was decreased in a total of the melanomas. Thus, HLA-linked immune response or immune suppression gene (s) appear to contribute to the susceptibility to human melanoma. There might be genetic differences between NM and ALM.