Whole-exome sequencing reveals the etiology of the rare primary hepatic mucoepidermoid carcinoma.
Whole-exome sequencing reveals the etiology of the rare primary hepatic mucoepidermoid carcinoma.
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全外显子组测序揭示罕见原发性肝粘液表皮样癌的病因
DOI：
10.1186/s13000-021-01086-3
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发表时间：
2021-04-08
影响因子：
2.6
通讯作者：
Liao W
中科院分区：
文献类型：
--
作者：
Hou P;Su X;Cao W;Xu L;Zhang R;Huang Z;Wang J;Li L;Wu L;Liao W
原发性肝粘液表皮样癌(HMEC)是一种罕见的肿瘤，其分子病因尚不清楚。CRTC1MAML2融合基因曾在原发涎腺上皮细胞中检测到，文献中常与涎腺上皮性上皮细胞癌有关。用荧光原位杂交(FISH)技术检测HMEC中CRTC1-MAML2融合基因的表达。用全外显子组测序和Sanger测序揭示HMEC的分子特征，并用公开数据进行分析。结果苏木精-伊红染色和免疫组织化学显示肿瘤细胞由恶性的表皮样恶性细胞和粘液细胞组成，提示诊断为HMEC。在原代HMEC中未检测到CRTC1-MAML2融合基因，通过测序鉴定了GNAS、KMT2C3和ELF3基因的体细胞突变。对公开资料的分析显示，2.1%的肝胆肿瘤存在体细胞性GNAS改变，并与寄生虫感染有关。还发现了FANCA、FANCI、FANCJ/BRIP1和FAN1基因的杂合性种系突变。家系调查证实家系中存在Fanconi贫血易感基因突变。结论首次提供了与Fanconi贫血基因突变和体细胞GNAS R201H突变相关的罕见HMEC的分子病因学证据。
BackgroundPrimary hepatic mucoepidermoid carcinoma (HMEC) is extremely rare and the molecular etiology is still unknown. TheCRTC1-MAML2fusion gene was previously detected in a primary HMEC, which is often associated with MEC of salivary gland in the literature.MethodsA 64-year-old male was diagnosed with HMEC based on malignant squamous cells and mucus-secreting cells in immunohistochemical examination. Fluorescence in situ hybridization (FISH) was used to detect theCRTC1-MAML2fusion gene in HMEC. Whole-exome sequencing and Sanger sequencing were used to reveal the molecular characteristics of HMEC and analysis was performed with public data. Pedigree investigation was performed to identify susceptibility genes.ResultsHematoxylin–eosin staining and immunohistochemistry revealed that the tumor cells were composed of malignant epidermoid malignant cells and mucous cells, indicating a diagnosis of HMEC. TheCRTC1-MAML2fusion gene was not detected in the primary HMEC, and somatic mutations inGNAS,KMT2CandELF3genes were identified by sequencing. Analyses of public data revealed somaticGNASalterations in 2.1% hepatobiliary tumors and relation with parasite infection. Heterozygous germline mutations ofFANCA,FANCI,FANCJ/BRIP1andFAN1genes were also identified. Pedigree investigation verified that mutation of Fanconi’s anemia susceptibility genes were present in the pedigree.ConclusionsHere we provide the first evidence of the molecular etiology of a rare HMEC associated with germline Fanconi’s anemia gene mutations and somatic GNAS R201H mutation.
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影响因子：
24.5
作者：
Farges, Olivier;Ferreira, Nelio;Paradis, Valerie
通讯作者：
Paradis, Valerie
影响因子：
3.5
作者：
LINARES, M;PASTOR, E;GRAU, E
通讯作者：
GRAU, E
DOI：
10.1093/bioinformatics/btr670
发表时间：
2012-02-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Boeva V;Popova T;Bleakley K;Chiche P;Cappo J;Schleiermacher G;Janoueix-Lerosey I;Delattre O;Barillot E
通讯作者：
Barillot E
影响因子：
0.6
作者：
Moul AE;Bejarano PA;Casillas J;Levi JU;Garcia-Buitrago MT
通讯作者：
Garcia-Buitrago MT
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N