Marian C, Scope A, Laud K, Friedman E, Pavlotsky F, Yakobson E, Bressac-de Paillerets B, Azizi E
Service de Génétique, Institut Gustave Roussy, Villejuif, France.
Br J Cancer. 2005 Jun 20;92(12):2278-85. doi: 10.1038/sj.bjc.6602629.
To gain insight into the molecular mechanisms involved in the inherited predisposition to melanoma and associated neural system tumours, 42 Jewish, mainly Ashkenazi, melanoma families with or without neural system tumours were genotyped for germline point mutations and genomic deletions at the CDKN2A/ARF and CDK4 loci. CDKN2A/ARF deletion detection was performed using D9S1748, an intragenic microsatellite marker. Allele dosage at the p14ARF locus was analysed by quantitative real-time PCR employing a TaqMan probe that anneals specifically to exon 1beta of the p14ARF gene. For detecting point mutations, dHPLC and direct sequencing of the coding sequences of CDKN2A/ARF and CDK4 was used. No germline alterations in any of the tested genes were detected among the families under study. We conclude that in the majority of Ashkenazi Jewish families, the genes tested are unlikely to be implicated in the predisposition to melanoma and associated neural system tumours.
为深入了解黑色素瘤及相关神经系统肿瘤遗传易感性所涉及的分子机制，对42个有或没有神经系统肿瘤的犹太（主要是德系犹太人）黑色素瘤家族进行了基因分型，以检测CDKN2A/ARF和CDK4基因座的种系点突变和基因组缺失。使用基因内微卫星标记D9S1748进行CDKN2A/ARF缺失检测。通过使用特异性退火至p14ARF基因外显子1β的TaqMan探针的定量实时PCR分析p14ARF基因座的等位基因剂量。为检测点突变，使用了dHPLC以及对CDKN2A/ARF和CDK4编码序列进行直接测序。在所研究的家族中未检测到任何受试基因的种系改变。我们得出结论，在大多数德系犹太人家族中，受试基因不太可能与黑色素瘤及相关神经系统肿瘤的易感性有关。
