Lang J, Boxer M, MacKie R M
Duncan Guthrie Institute of Medical Genetics, Royal Hospital for Sick Children and University of Glasgow, Glasgow, Scotland, U.K.
Br J Dermatol. 2005 Dec;153(6):1121-5. doi: 10.1111/j.1365-2133.2005.06846.x.
Up to 5% of patients with melanoma have a family history of a first-degree relative also being affected.
To study such families for germline mutations, to help clarify the gene-environment interaction in melanoma aetiology.
Thirty-two families in Scotland with melanoma in two or more first-degree relatives are reported for the first time. Peripheral blood DNA was extracted, and denaturing high-performance liquid chromatography analysis performed on exons 1alpha and 2 of the CDKN2A gene and their splice junctions. The coding sequences and splice junctions of these exons were sequenced in all samples as confirmation of the chromatographic pattern observed.
Seven of the 32 melanoma families (22%) have CDKN2A mutations. One mutation, H83N, which has not previously been described in melanoma families, was found in one family. In addition, two families have R112G mutations, one family has a G67R mutation, one has an exon 1alpha 24-bp duplication where bases 9-32 are duplicated between bases 32 and 33, and two families have M53I mutations, bringing the total of known Scottish families with the M53I mutation to six.
This study brings the total of Scottish families investigated for germline mutations to 48, and strongly suggests that the M53I mutation originated in Scotland.
高达5%的黑色素瘤患者有一级亲属也患黑色素瘤的家族病史。
研究此类家族的种系突变，以帮助阐明黑色素瘤病因中的基因-环境相互作用。
首次报告了苏格兰的32个家族，其中两个或更多一级亲属患有黑色素瘤。提取外周血DNA，并对CDKN2A基因的1α和2外显子及其剪接位点进行变性高效液相色谱分析。对所有样本的这些外显子的编码序列和剪接位点进行测序，以确认观察到的色谱图。
32个黑色素瘤家族中有7个（22%）存在CDKN2A突变。在一个家族中发现了一种此前未在黑色素瘤家族中描述过的突变H83N。此外，两个家族有R112G突变，一个家族有G67R突变，一个家族有1α外显子24bp重复，即9至32位碱基在32和33位碱基之间重复，两个家族有M53I突变，使已知有M53I突变的苏格兰家族总数达到6个。
本研究使接受种系突变调查的苏格兰家族总数达到48个，并强烈表明M53I突变起源于苏格兰。
