匈牙利多发性原发性黑色素瘤患者的基因分型分析。

Genotype analysis in Hungarian patients with multiple primary melanoma.

作者信息

Hatvani Zsófia, Brodszky Valentin, Mazán Mercédesz, Pintér Dóra, Hársing Judit, Tóth Veronika, Somlai Beáta, Kárpáti Sarolta

机构信息

Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, Budapest, Hungary.

出版信息

Exp Dermatol. 2014 May;23(5):361-4. doi: 10.1111/exd.12382.

DOI:10.1111/exd.12382

PMID:24660985

Abstract

Multiple primary melanoma patients (MPMps) have better prognosis and are more prone to genetic predisposition than single melanoma patients. We aimed to compare genetic background (CDKN2A, CDK4, MITF, MC1R) of 43 Hungarian MPMps with their clinicopathological data. We observed a higher rate of synchronous first and second melanoma (MM) (49%) and a higher frequency of non-melanoma tumor co-occurrence (42%) than reported previously. CDKN2A mutation frequency was 4.7% (E69G, R99P). We identified a new human MC1R variant (D117G) and reported MC1R variant distributions in Hungarian MMs for the first time. The rare R163Q was exceptionally common among Hungarian MPMps, a variant otherwise frequent in Asia, but not in Europe. MC1R 'R' carriers showed histopathological signs of a more progressive disease than 'r' carriers did; however, tumor-infiltrating lymphocytes (TILs) in their second melanomas occurred significantly more frequently. Calculating 5-year overall survival, 'R' carriers showed more unfavourable prognosis (87%) than 'r' carriers did (95%).

摘要

多原发性黑色素瘤患者（MPMps）比单发性黑色素瘤患者预后更好，且更易发生遗传易感性。我们旨在比较43例匈牙利MPMps患者的基因背景（CDKN2A、CDK4、MITF、MC1R）与其临床病理数据。我们观察到，与之前报道相比，同时发生的原发性和继发性黑色素瘤（MM）发生率更高（49%），非黑色素瘤肿瘤共发频率更高（42%）。CDKN2A突变频率为4.7%（E69G、R99P）。我们鉴定出一种新的人类MC1R变体（D117G），并首次报告了匈牙利MM中MC1R变体的分布情况。罕见的R163Q在匈牙利MPMps患者中异常常见，该变体在亚洲常见，但在欧洲不常见。与“r”携带者相比，MC1R“R”携带者的疾病组织病理学表现更具侵袭性；然而，其继发性黑色素瘤中的肿瘤浸润淋巴细胞（TILs）出现频率明显更高。计算5年总生存率，“R”携带者的预后（87%）比“r”携带者（95%）更差。