The Association between MC1R Genotype and BRAF Mutation Status in Cutaneous Melanoma: Findings from an Australian Population
The Association between MC1R Genotype and BRAF Mutation Status in Cutaneous Melanoma: Findings from an Australian Population
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DOI：
10.1038/jid.2009.182
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发表时间：
2010-01-01
影响因子：
6.5
通讯作者：
Whiteman, David C.
中科院分区：
文献类型：
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作者：
Hacker, Elke;Hayward, Nicholas K.;Whiteman, David C.
越来越多的流行病学和分子证据表明皮肤黑色素瘤是通过多种因果途径产生的。本研究的目的是探索一系列基于人群的黑色素瘤患者的种系突变和体细胞突变之间的关系，以重塑和完善黑色素瘤的发散途径模型。对从 123 名澳大利亚患者收集的黑色素瘤进行了黑皮质素-1 受体 (MC1R) 变异以及 BRAF 和 NRAS 基因突变的分析。从所有患者中系统地收集了详细的表型和阳光照射数据。我们发现 BRAF 突变黑色素瘤明显更可能来自年轻患者和痣计数高的患者，并且更有可能出现在具有邻近痣残留的黑色素瘤中。相反，一生中经常暴露在阳光下的人患 BRAF 突变黑色素瘤的可能性显着降低。我们观察到该群体黑色素瘤中种系 MC1R 状态与体细胞 BRAF 突变之间没有关联。 BRAF 突变黑色素瘤与其他皮肤黑色素瘤具有不同的起源。这些数据支持黑色素瘤的不同途径假说，这可能需要重新评估有针对性的癌症预防活动。
There is increasing epidemiological and molecular evidence that cutaneous melanomas arise through multiple causal pathways. The purpose of this study was to explore the relationship between germline and somatic mutations in a population-based series of melanoma patients to reshape and refine the divergent pathway model for melanoma. Melanomas collected from 123 Australian patients were analyzed for melanocortin-1 receptor (MC1R) variants and mutations in the BRAF and NRAS genes. Detailed phenotypic and sun exposure data were systematically collected from all patients. We found that BRAF-mutant melanomas were significantly more likely from younger patients and those with high nevus counts, and were more likely in melanomas with adjacent neval remnants. Conversely, BRAF-mutant melanomas were significantly less likely in people with high levels of lifetime sun exposure. We observed no association between germline MC1R status and somatic BRAF mutations in melanomas from this population. BRAF-mutant melanomas have different origins from other cutaneous melanomas. These data support the divergent pathways hypothesis for melanoma, which may require a reappraisal of targeted cancer prevention activities.