Büttner C, Henz B M, Welker P, Sepp N T, Grabbe J
Department of Dermatology, Charité, Humboldt University, Berlin, Germany.
J Invest Dermatol. 1998 Dec;111(6):1227-31. doi: 10.1046/j.1523-1747.1998.00414.x.
Mastocytosis represents a mast cell proliferative disease that generally runs a benign clinical course, with spontaneous remissions mostly by puberty in childhood-onset disease, although rare forms, particularly in adult-onset disease, can be associated with (pre)malignant hematologic disorders and very rarely present as mast cell leukemia or malignant mastocytosis. Reasons for this divergent clinical behavior of childhood- versus adult-onset disease are unknown. Recently, two activating mutations in the intracellular domain of the proto-oncogene c-kit, which encodes a tyrosine kinase receptor for the mast cell growth factor stem cell factor, have been detected in the human leukemic mast cell line HMC-1. We have therefore studied lesional skin biopsies from patients with adult- and childhood-onset indolent mastocytosis for the presence of these codon 560 and 816 mutations. C-kit coding DNA sequences were amplified and analyzed by mutation-specific restriction analyses, and mutated polymerase chain reaction products were additionally cloned and sequenced. The codon 816 mutation was found in all six samples from adult patients, but not in any of the 11 specimens from children. In addition, the codon 560 mutation could be demonstrated for the first time in indolent mastocytosis, namely in two of four specimens from adult patients, but not in those from two children. These data thus provide a possible explanation for the divergent clinical behavior of adult- versus childhood-onset indolent mastocytosis, with the first being associated with an activating mutation, possibly as part of a neoplastic process, and the latter representing most likely a reactive process of an as yet unknown pathogenesis.
肥大细胞增多症是一种肥大细胞增殖性疾病，通常呈良性临床病程，儿童期发病的疾病大多在青春期自发缓解，不过罕见类型，尤其是成人期发病的疾病，可能与（前）恶性血液系统疾病相关，极少数情况下表现为肥大细胞白血病或恶性肥大细胞增多症。儿童期与成人期发病疾病这种不同临床行为的原因尚不清楚。最近，在人白血病肥大细胞系HMC-1中检测到原癌基因c-kit细胞内结构域的两个激活突变，c-kit编码肥大细胞生长因子干细胞因子的酪氨酸激酶受体。因此，我们研究了成人期和儿童期发病的惰性肥大细胞增多症患者的皮损活检标本，以检测这些密码子560和816突变的存在情况。通过突变特异性限制性分析对c-kit编码DNA序列进行扩增和分析，对突变的聚合酶链反应产物另外进行克隆和测序。在所有6份成人患者样本中均发现了密码子816突变，但11份儿童样本中均未发现。此外，首次在惰性肥大细胞增多症中证实了密码子560突变，即在4份成人患者标本中有2份存在该突变，而2份儿童标本中未发现。这些数据因此为成人期与儿童期发病的惰性肥大细胞增多症的不同临床行为提供了一种可能的解释，前者与激活突变相关，可能是肿瘤形成过程的一部分，而后者很可能代表一种发病机制尚不清楚的反应性过程。
