Mantelli Michela, Barile Monica, Ciotti Paola, Ghiorzo Paola, Lantieri Francesca, Pastorino Lorenza, Catricalà Caterina, Torre Gabriella Della, Folco Ugo, Grammatico Paola, Padovani Laura, Pasini Barbara, Rovini Dario, Queirolo Paola, Rainero Maria Luisa, Santi Pier Luigi, Sertoli Roberto M, Goldstein Alisa M, Bianchi-Scarrà Giovanna
Dipartimento di Oncologia, Biologia e Genetica, Università degli Studi di Genova, Genova, Italy.
Am J Med Genet. 2002 Jan 22;107(3):214-21.
CDKN2A germline mutation frequency estimates are commonly based on families with several melanoma cases. When we started counseling in a research setting on gene susceptibility analysis in northern and central Italy, however, we mostly found small families with few cases. Here we briefly characterize those kindred, estimate CDKN2A/CDK4 mutation test yields, and provide indications on the possibility of implementing formal DNA testing for melanoma-prone families in Italy. In September 1995 we started genetic counseling in a research setting at our Medical Genetics Center. Screening for CDKN2A/CDK4 mutations was performed on families with two melanoma patients, one of whom was younger than 50 years at onset, the other complying with one of the following: 1) being a first-degree relative, 2) having an additional relative with pancreatic cancer, or 3) having multiple primary melanomas. Sixty-two of 67 (80%) melanoma cases met our criteria. Four previously described CDKN2A mutations (G101W, R24P, V126D, and N71S) were found in 21 of the 62 families (34%) with a high prevalence of G101W (18/21). The percentage of families with two melanoma cases/family harboring a mutation was low (7%, 2/27), but rose to 45% (9/20) if one of the melanoma patients carried multiple melanomas or if pancreatic cancer was present in that family. In the 15 families with three melanoma cases the presence of a mutation was higher (67%, 10/15) and reached 100% in the 4 families with four or more melanoma cases. Our results suggest that CDKN2A/CDK4 counseling-based mutational analysis may be reasonably efficient also for families with two melanoma cases, if one patient carries multiple melanomas or if pancreatic cancer is present in the family.
CDKN2A种系突变频率估计通常基于有几例黑色素瘤病例的家族。然而，当我们开始在意大利北部和中部的研究环境中就基因易感性分析进行咨询时，我们大多发现病例数少的小家族。在此，我们简要描述这些家族，估计CDKN2A/CDK4突变检测的阳性率，并就意大利对黑色素瘤易感家族实施正式DNA检测的可能性提供指导。1995年9月，我们在医学遗传学中心的研究环境中开始了遗传咨询。对有两名黑色素瘤患者的家族进行CDKN2A/CDK4突变筛查，其中一名患者发病年龄小于50岁，另一名患者符合以下条件之一：1）为一级亲属，2）有另一名患胰腺癌的亲属，或3）有多发性原发性黑色素瘤。67例黑色素瘤病例中有62例（80%）符合我们的标准。在62个家族中的21个（34%）发现了4种先前描述的CDKN2A突变（G101W、R24P、V126D和N71S），其中G101W的发生率很高（18/21）。每个家族有两名黑色素瘤病例且携带突变的家族比例较低（7%，2/27），但如果其中一名黑色素瘤患者有多发性黑色素瘤或该家族中有胰腺癌患者，则该比例升至45%（9/20）。在有三例黑色素瘤病例的15个家族中，突变的存在率更高（67%，10/15），在有四例或更多黑色素瘤病例的4个家族中达到100%。我们的结果表明，如果一名患者有多发性黑色素瘤或家族中有胰腺癌患者，基于CDKN2A/CDK4咨询的突变分析对于有两名黑色素瘤病例的家族可能也相当有效。
