Palmedo Gabriele, Hantschke Markus, Rütten Arno, Mentzel Thomas, Hügel Heino, Flaig Michael J, Yazdi Amir S, Sander Christian A, Kutzner Heinz
Dermatopathologische Gemeinschaftspraxis, Friedrichshafen, Germany.
J Cutan Pathol. 2004 Mar;31(3):266-70. doi: 10.1111/j.0303-6987.2003.00179.x.
BRAF, a serine/threonine kinase, is a component of the retrovirus-associated sequence (RAS)-RAF-extracellular-regulated protein kinase (ERK)-MAP kinase signal transduction pathway mediating signals from RAS to ERK. The T1796A single point mutation in exon 15 of the BRAF gene has recently been reported in a high percentage of malignant melanomas and benign melanocytic lesions such as congenital nevi, compound nevi, intradermal nevi and dysplastic nevi. The T1796A mutation has been shown to promote cell proliferation.
We screened 21 Spitz nevi and six spitzoid malignant melanomas for the presence of the T1796A BRAF mutation.
The T1796A BRAF mutation could not be detected in any of the 21 Spitz nevi but was present in two of the six spitzoid malignant melanomas.
Our results, in conjunction with data from a previous investigation, suggest that the melanocytic proliferation of Spitz nevi might be induced by components of the RAS-RAF-ERK-MAP kinase pathway different from BRAF, possibly combined with other genetic aberrations. The lack of the T1796A BRAF mutation might be of practical importance in distinguishing Spitz nevi from other melanocytic lesions simulating Spitz nevi as a part of a future complex diagnostic assay.
BRAF是一种丝氨酸/苏氨酸激酶，是逆转录病毒相关序列（RAS）-RAF-细胞外调节蛋白激酶（ERK）-丝裂原活化蛋白激酶信号转导途径的一个组成部分，介导从RAS到ERK的信号传导。最近有报道称，BRAF基因第15外显子中的T1796A单点突变在高比例的恶性黑色素瘤和良性黑素细胞病变（如先天性痣、复合痣、皮内痣和发育异常痣）中存在。T1796A突变已被证明可促进细胞增殖。
我们对21例Spitz痣和6例Spitz样恶性黑色素瘤进行了T1796A BRAF突变检测。
21例Spitz痣中均未检测到T1796A BRAF突变，但6例Spitz样恶性黑色素瘤中有2例存在该突变。
我们的结果与先前一项研究的数据表明，Spitz痣的黑素细胞增殖可能由不同于BRAF的RAS-RAF-ERK-丝裂原活化蛋白激酶途径的成分诱导，可能与其他基因异常相结合。T1796A BRAF突变的缺失在将Spitz痣与其他模拟Spitz痣的黑素细胞病变区分开来方面可能具有实际意义，可作为未来复杂诊断检测的一部分。
