Distinct non-clock-like signatures of the basal cell carcinomas from three sisters with a lethal Gorlin-Goltz syndrome.
Distinct non-clock-like signatures of the basal cell carcinomas from three sisters with a lethal Gorlin-Goltz syndrome.
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DOI：
10.1186/s12920-022-01324-7
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发表时间：
2022-08-05
影响因子：
2.7
通讯作者：
Zhang, Qiaoan
中科院分区：
文献类型：
--
作者：
Ye, Lihua;Wang, Li;Peng, Kexin;Fang, Ou;Tian, Zhen;Li, Caihua;Fu, Xiaopeng;Chen, Qingdong;Chen, Jia;Luan, Jing;Zhang, Zhenghua;Zhang, Qiaoan
Gorlin-Goltz syndrome (GS) is an inherited disease characterized by predisposition to basal cell carcinomas (BCCs) and various developmental defects, whose numerous disease-causing PTCH1 mutations have been identified in the hedgehog (Hh) signaling pathway. In this study, whole exome sequencing was used to screen for both somatic and germline deleterious mutations in three sisters with a lethal GS. The mutations we found were confirmed by subcloning and Sanger sequencing of the genomic DNA. RNA-seq was performed to profile gene expression in paired BCCs samples and the expression levels for selected genes were validated by quantitative PCR. The clinical and histopathologic features were analyzed for the proband in the three-generation GS family. We identified the insertion mutation PTCH1 c.1341dupA (p. L448Tfs*49), which segregated with BCC phenotype and contributed to the death of two in four patients from a Chinese family with GS. Compared with adjacent non-cancerous tissues (ANCT), four second-hit mutations were found in four of the six pairs of BCC from three patients. Of note, somatic genomic alterations in all six BCC samples were mainly clustered into non-clock-like Signature 7 (ultraviolet mutagenesis) and 11 (related to certain alkylating agents). Both RNA-seq and quantitative RT-PCR confirmed that the mRNA levels of PTCH1 and its effector GLI1 were markedly upregulated in six pairs of BCC samples versus ANCT. The distinct non-clock-like signatures of BCCs indicated that GS was not a life-threatening illness. The main reasons for untimely death of GS patients were PTCH1 mutation, exposure to intense ultraviolet radiationand the poor economic conditions. The online version contains supplementary material available at 10.1186/s12920-022-01324-7.
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影响因子：
5.6
作者：
Pellegrini C;Maturo MG;Di Nardo L;Ciciarelli V;Gutiérrez García-Rodrigo C;Fargnoli MC
通讯作者：
Fargnoli MC
DOI：
10.1016/j.omtn.2020.10.033
发表时间：
2021-03-05
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Chong W;Wang Z;Shang L;Jia S;Liu J;Fang Z;Du F;Wu H;Liu Y;Chen Y;Chen H
通讯作者：
Chen H
影响因子：
12.3
作者：
McLaren W;Gil L;Hunt SE;Riat HS;Ritchie GR;Thormann A;Flicek P;Cunningham F
通讯作者：
Cunningham F
DOI：
10.1007/978-3-319-56017-5_3
发表时间：
2017-01-01
期刊：
ULTRAVIOLET LIGHT IN HUMAN HEALTH, DISEASES AND ENVIRONMENT
影响因子：
--
作者：
Liu-Smith, Feng;Jia, Jinjing;Zheng, Yan
通讯作者：
Zheng, Yan
影响因子：
4
作者：
Wilding, Anna;Ingham, Sarah Louise;Evans, D. Gareth
通讯作者：
Evans, D. Gareth