Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1
Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1
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DOI：
10.1038/ng.780
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发表时间：
2011-04-01
期刊：
影响因子：
30.8
通讯作者：
Lane, E. Birgitte
中科院分区：
文献类型：
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作者：
Goudie, David R.;D'Alessandro, Mariella;Lane, E. Birgitte
多发性自愈性鳞状上皮瘤（MSSE），也称为Ferguson-Smith病（FSD），是一种常染色体显性皮肤癌疾病，其特征为多发性鳞状癌样局部浸润性皮肤肿瘤，在自发消退前快速生长数周，留下疤痕（1，2）。使用外显子阵列捕获技术对9号染色体上的疾病位点进行保守估计（24.2 Mb）的高通量基因组测序，在三个不相关的家族中鉴定了TGFBR 1的独立突变。随后的TGFBR 1双脱氧测序确定了18个受影响的家庭中的11个不同的单等位基因突变，坚定地建立TGFBR 1作为致病基因。序列变体的性质，包括细胞外配体结合结构域中的突变和激酶结构域中的一系列截短突变，表明功能丧失型TGFBR 1突变和MSSE之间存在明确的基因型-表型相关性。这将MSSE与马凡氏综合征相关疾病区分开来，马凡氏综合征相关疾病中TGFBR 1的错义突变导致血管受累的发育缺陷，但没有报道的癌症易感性。
Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith disease (FSD), is an autosomal-dominant skin cancer condition characterized by multiple squamous-carcinoma-like locally invasive skin tumors that grow rapidly for a few weeks before spontaneously regressing, leaving scars(1,2). High-throughput genomic sequencing of a conservative estimate (24.2 Mb) of the disease locus on chromosome 9 using exon array capture identified independent mutations in TGFBR1 in three unrelated families. Subsequent dideoxy sequencing of TGFBR1 identified 11 distinct monoallelic mutations in 18 affected families, firmly establishing TGFBR1 as the causative gene. The nature of the sequence variants, which include mutations in the extracellular ligand-binding domain and a series of truncating mutations in the kinase domain, indicates a clear genotype-phenotype correlation between loss-of-function TGFBR1 mutations and MSSE. This distinguishes MSSE from the Marfan syndrome-related disorders in which missense mutations in TGFBR1 lead to developmental defects with vascular involvement but no reported predisposition to cancer.