Assessment of clinical parameters associated with mutational status in metastatic malignant melanoma: a single-centre investigation of 141 patients
Assessment of clinical parameters associated with mutational status in metastatic malignant melanoma: a single-centre investigation of 141 patients
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DOI：
10.1111/bjd.12140
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发表时间：
2013-04-01
影响因子：
10.3
通讯作者：
Kurschat, P.
中科院分区：
文献类型：
--
作者：
Schlaak, M.;Bajah, A.;Kurschat, P.
突变的、组成型激活的BRAF蛋白的抑制剂在临床试验中显示出治疗转移性黑色素瘤的有效性。突变分析，特别是BRAF，NRAS和KIT基因是必不可少的，以确定患者适合有针对性的治疗，并已被引入到常规patient care.Objectives相关的突变状态与临床参数，包括年龄，皮肤类型，黑色素细胞痣，原发肿瘤的位置，慢性太阳损伤和暴露于紫外线（UV）照射的数量。总体目标是定义基因突变可能性增加或减少的亚组。此外，激活BRAF突变对临床course.Methods的影响进行了调查，在一个单中心，回顾性的方法，突变分析转移性恶性黑色素瘤患者。临床参数与分子结果相关。总的阳光负荷得分进行了评估，使用一个有效的标准化questionnaire.Results的分析包括141例转移性黑色素瘤患者。44%的患者有激活的BRAF突变，并且明显比野生型BRAF或NRAS突变的患者年轻。仅在3%的患者中检测到KIT突变。BRAF突变的黑色素瘤优先发生在身体间歇性暴露于阳光的区域，患者的黑色素细胞痣明显更多。一旦患者进展到IV期疾病，生存时间是相同的BRAF突变和BRAF野生型tumors.Conclusions BRAF基因的突变与年轻的年龄，黑色素细胞痣和肿瘤的位置在间歇性紫外线暴露的皮肤。慢性光损伤的迹象并不表明突变状态。具有BRAF突变的转移性黑色素瘤患者表现出不显著的后期进展至IV期疾病的趋势，但一旦出现转移，其预后与BRAF野生型肿瘤相同。
Background Inhibitors of the mutated, constitutively activated BRAF protein have shown efficacy in the treatment of metastatic melanoma in clinical trials. Mutation analysis especially of the BRAF, NRAS and KIT genes is essential to identify patients suitable for targeted therapies and has been introduced into routine patient care.Objectives To correlate mutational status with clinical parameters including age, skin type, number of melanocytic naevi, primary tumour location, chronic sun damage and exposure to ultraviolet (UV) irradiation. The overall aim was to define subgroups with an increased or decreased likelihood of gene mutations. Additionally, the impact of activating BRAF mutations on clinical course was investigated.Methods In a single-centre, retrospective approach, mutation analysis was performed on patients with metastatic malignant melanoma. Clinical parameters were correlated with molecular findings. The total sun-burden score was assessed using a validated standardized questionnaire.Results The analysis included 141 patients with metastatic melanoma. Forty-four per cent of patients had activating BRAF mutations and were significantly younger than patients with wild-type BRAF or with NRAS mutations. KIT mutations were detected in only 3% of the patients. BRAF-mutated melanomas developed preferentially in intermittently sun-exposed areas of the body, and patients had significantly more melanocytic naevi. Once patients had progressed into stage IV disease, survival times were identical for those with BRAF-mutated and BRAF wild-type tumours.Conclusions Mutations of the BRAF gene are correlated with younger age, a higher number of melanocytic naevi and a tumour location in intermittently UV-exposed skin. Signs of chronic photodamage are not indicative of mutational status. Patients with metastatic melanoma with BRAF mutations showed a nonsignificant tendency to progress later to stage IV disease, but once metastases were present the prognosis was identical to that with BRAF wild-type tumours.