Ruiz A, Puig S, Malvehy J, Lázaro C, Lynch M, Gimenez-Arnau A M, Puig L, Sánchez-Conejo J, Estivill X, Castel T
Medical and Molecular Genetics Centre-IRO, Hospital Duran i Reynals, Barcelona, Catalonia, Spain.
J Med Genet. 1999 Jun;36(6):490-3.
The CDKN2A gene has been implicated in cutaneous malignant melanoma (CMM) in about 40% of families with linkage to chromosome 9p21, while a small proportion of families have mutations in the CDK4 gene. In order to estimate the importance of these genes in the predisposition to CMM in Spanish families and patients we have analysed, by SSCA, a total of 56 subjects belonging to 34 CMM families, and nine patients with multiple CMM and other neoplasia. We have detected germline CDKN2A mutations in six out of the 34 families (17%). A frameshift mutation (358delG) and four missense mutations (G59V, G101W (two cases), D84Y, and R87W) were identified. Five CMM patients from different families (14%) carried the A148T variant, which is known not to affect p16 activity. No mutations were detected in the patients with multiple CMM or other neoplasms. We have not found mutations either in exon 1 beta of the CDKN2A gene or in exon 2A of CDK4. Linkage analysis of the 9p21 region showed exclusion for one of the families for CMM and for four families for CMM/dysplastic naevi. This study indicates a small role for CDKN2A in Spanish CMM families and suggests that other genes are also responsible for CMM predisposition.
在约40%与9号染色体p21区域连锁的家族性皮肤恶性黑色素瘤（CMM）中，CDKN2A基因与之相关，而一小部分家族的CDK4基因存在突变。为了评估这些基因在西班牙家族性CMM患者易感性中的重要性，我们通过单链构象多态性分析（SSCA），对34个CMM家族的56名成员以及9名患有多发性CMM和其他肿瘤的患者进行了分析。我们在34个家族中的6个（17%）检测到了种系CDKN2A突变。鉴定出一个移码突变（358delG）和四个错义突变（G59V、G101W（两例）、D84Y和R87W）。来自不同家族的5名CMM患者（14%）携带A148T变异体，已知该变异体不影响p16活性。在患有多发性CMM或其他肿瘤的患者中未检测到突变。我们在CDKN2A基因的1β外显子或CDK4的2A外显子中也未发现突变。9p21区域的连锁分析显示，一个家族排除了CMM，四个家族排除了CMM/发育异常痣。这项研究表明CDKN2A在西班牙CMM家族中的作用较小，并提示其他基因也与CMM易感性有关。
