RET mutation p.S891A in a Chinese family with familial medullary thyroid carcinoma and associated cutaneous amyloidosis binding OSMR variant p.G513D.
RET mutation p.S891A in a Chinese family with familial medullary thyroid carcinoma and associated cutaneous amyloidosis binding OSMR variant p.G513D.
复制标题
一个患有家族性甲状腺髓样癌和相关皮肤淀粉样变性的中国家族中的 RET 突变 p.S891A 结合 OSMR 变异 p.G513D。
DOI：
10.18632/oncotarget.4992
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发表时间：
2015-10-20
期刊：
影响因子：
--
通讯作者：
Ma JM
中科院分区：
文献类型：
--
作者：
Qi XP;Zhao JQ;Chen ZG;Cao JL;Du J;Liu NF;Li F;Sheng M;Fu E;Guo J;Jia H;Zhang YM;Ma JM
家族性甲状腺髓样癌(FMTC)伴发皮肤淀粉样变性(CA)与RET或OSMR/IL31RA基因突变的关系尚未见报道。在这项研究中，我们调查了一个中国人FMTC/CA家系，发现在17名家庭成员中有6名成员发生了RET c.2671T>；G(p.S891A)突变。6例P.S891A突变携带者中有3例表现为甲状腺髓样癌(MTC)。其中3例(2例伴MTC，1例不伴MTC)被诊断为合并苔藓/黄斑双相CA。我们还在五个成员中发现了一个新的RET变异体c.1573C>；T(p.R525W)。其中三名携带者没有甲状腺/皮肤或基础血清/刺激性降钙素异常的证据。体外细胞增殖实验表明，p.R525W对RET p.S891A的致癌活性有轻微的促进作用，而p.R525W单独作用对细胞增殖无明显影响。同时，我们在7个成员中发现了一个新的OSMR变异体C.1538G>；A(p.G513D)。我们注意到3例伴有CA的OSMR p.G513D携带者也存在RET p.S891A突变。我们的研究表明，RET p.S891A突变与OSMR p.G513D相结合可能是一种新的表现为FMTC和CA的表型。
There are no reports on the relationship between familial medullary thyroid carcinoma (FMTC) associated with cutaneous amyloidosis (CA) and RET or OSMR/IL31RA gene mutations. In this study, we investigated a Chinese family with FMTC/CA and found a recurrent RET c.2671T>G (p.S891A) mutation in six of 17 family members. Three of the six p.S891A mutation carriers presented with medullary thyroid carcinoma (MTC). Of them, three (two with and one without MTC) were diagnosed as having combined lichen/macular biphasic CA. We also identified a novel RET variant, c.1573C>T (p.R525W) in five members. Of them, three carriers had no evidence of thyroid/skin or basal serum/stimulated calcitonin abnormalities. In vitro cell proliferation assay indicated that oncogenic activity of RET p.S891A was slightly enhanced by p.R525W, whereas p.R525W alone had no effect on cell proliferation. Meanwhile, we identified a novel OSMR variant, c.1538G>A (p.G513D) in seven members. We noticed that three OSMR p.G513D carriers presenting with CA also had the RET p.S891A mutation. Our investigation indicated that the RET p.S891A mutation combined with OSMR p.G513D may underlie a novel phenotype manifesting as FMTC and CA.