HOMOZYGOUS DELETIONS WITHIN HUMAN-CHROMOSOME BAND-9P21 IN MELANOMA
HOMOZYGOUS DELETIONS WITHIN HUMAN-CHROMOSOME BAND-9P21 IN MELANOMA
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DOI：
10.1073/pnas.89.21.10557
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发表时间：
1992-11-01
影响因子：
11.1
通讯作者：
DRACOPOLI, NC
中科院分区：
文献类型：
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作者：
FOUNTAIN, JW;KARAYIORGOU, M;DRACOPOLI, NC
遗传学研究表明染色体臂 9p 上的一个基因早期参与了皮肤黑色素瘤的发展。我们进行了杂合性丢失研究来证实这些原始发现并确定 9p 最频繁重排或删除的区域。分析了八个标记物，包括（从 9pter 到近端 9q）D9S33、β-干扰素 (IFNB1) 基因座、α-干扰素 (IFNA) 基因簇、D9S126、D9S3、D9S19、糖蛋白 4β-半乳糖基转移酶 (GGTB2) 基因和精氨基琥珀酸 合成酶假基因 3 (ASSP3)。在 14 个有信息的转移性黑色素瘤肿瘤和细胞系 DNA 中的 12 个 (86%) 中发现这些基因座中的两个或多个位点半合子减少，并且在 20 个黑色素瘤细胞系中的 2 个 (10%) 中观察到标记 D9S126 的纯合缺失。这些发现导致在 9p21 上鉴定出一个 2-3 兆碱基的小关键区域，其中可能存在假定的黑色素瘤肿瘤抑制基因。几个 9p 候选基因，包括 IFNB1、IFNA 基因簇、GGTB2 和酪氨酸酶相关蛋白 (TYRP) 位点，均已作为潜在靶标被排除，因为它们位于纯合删除区域之外。
Genetic studies have implicated the early involvement of a gene on chromosome arm 9p in the development of cutaneous melanoma. We have performed loss-of-heterozygosity studies to confirm these original findings and identify the most frequently rearranged or deleted region of 9p. Eight markers were analyzed, including (from 9pter to proximal 9q) D9S33, the beta-interferon (IFNB1) locus, the alpha-interferon (IFNA) gene cluster, D9S126, D9S3, D9S19, the glycoprotein 4beta-galactosyltransferase (GGTB2) gene, and the argininosuccinate synthetase pseudogene 3 (ASSP3). Two or more of these loci were found to be hemizygously reduced in 12 of 14 (86%) informative metastatic melanoma tumor and cell line DNAs, and homozygous deletions of the marker D9S126 were observed in 2 of 20 (10%) melanoma cell lines. These findings have resulted in the identification of a small critical region of 2-3 megabases on 9p21 in which a putative melanoma tumor-suppressor gene appears likely to reside. Several 9p candidate genes, including IFNB1, the IFNA gene cluster, GGTB2, and the tyrosinase-related protein (TYRP) locus, have all been eliminated as potential targets because they are located outside of the homozygously deleted regions.