BRAF mutation -: A frequent event in benign, atypical, and malignant melanocytic lesions of the skin
BRAF mutation -: A frequent event in benign, atypical, and malignant melanocytic lesions of the skin
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DOI：
10.1097/00000372-200310000-00001
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发表时间：
2003-10-01
影响因子：
1.1
通讯作者：
González, S
中科院分区：
文献类型：
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作者：
Uribe, P;Wistuba, II;González, S
最近在皮肤黑色素瘤中检测到BRAF突变的频率很高(66%)。所有这些突变都是激活的，密码子599(V599E)上的单个替换(T1796A)占90%以上。为了研究目前提出的黑素细胞序贯恶变过程中这些突变发生的阶段，采用从福尔马林固定和石蜡包埋的组织中提取的DNA和基于两轮PCR-RFLP的策略，对来自63名不同患者的22例良性黑色素细胞痣、23例黑素细胞不典型痣和25例原发性皮肤黑色素瘤进行了BRAF突变检测。对样本的子集进行了测序，以进行突变确认。16例良性(73%)和11例不典型(52%)黑色素细胞痣和13例黑色素瘤(56%)存在BRAF基因599位密码子突变，三种类型的皮损之间差异无统计学意义。在与具有BRAF突变的黑素细胞损伤相邻的显微解剖的表皮角质形成细胞中没有发现突变。在恶性黑色素瘤中，BPAF突变状态与年龄、阳光暴露和Clark‘s水平之间没有相关性。然而，仅比较不典型痣和黑色素瘤皮损，男性患者的BRAF突变频率(78%)显著高于女性患者(35%)(P=0.0194)。在18例突变样本中有17例检测到上述T1796A点突变，在1例黑色素瘤病例中检测到一种新的突变，该突变包括用缬氨酸取代赖氨酸(GT1795-96AA)。我们发现皮肤良性化生细胞病变中599密码子的BRAF突变频率很高，这表明该突变本身不足以发生恶性转化。
BRAF mutations have recently been detected with a high frequency (66%) in cutaneous melanoma. All those mutations are activating, with a single substitution (T1796A) at codon 599 (V599E) accounting for over 90%. To investigate the stage in which those mutations occur in the currently proposed sequential malignant transformation of melanocytes, 22 benign melanocytic nevi, 23 melanocytic atypical nevi, and 25 primary cutaneous melanoma from 63 different patients were examined for BRAF mutations using DNA extracted from microdissected formalin-fixed and paraffin-embedded tissues, and a two-round PCR-RFLP-based strategy. A subset of samples was sequenced for mutation confirmation. Sixteen benign (73%) and eleven atypical (52%) melanocytic nevi, and thirteen melanoma (56%) demonstrated BRAF mutations at codon 599, and no statistically significant differences were detected among all three types of lesions. No mutations were demonstrated in microdissected epidermal keratinocytes adjacent to melanocytic lesions having BRAF mutations. No correlation was detected between BPAF mutational status and age, sun exposure, and Clark's level in malignant melanoma. However, comparing only atypical nevi and melanoma lesions the frequency of BRAF mutation is significantly greater in male (78%) than female (35%) patients (P = 0.0194). The previously described T1796A point mutation was detected in 17 of 18 mutated samples, and a novel mutation consisting of a substitution of valine for lysine (GT1795-96AA) was detected in one melanoma case. Our findings of a high frequency of BRAF mutations at codon 599 in benign metanocytic lesions of the skin indicate that this mutation is not sufficient by itself for malignant transformation.