PMID- 33832503 OWN - NLM STAT- MEDLINE DCOM- 20211117 LR - 20221207 IS - 1746-1596 (Electronic) IS - 1746-1596 (Linking) VI - 16 IP - 1 DP - 2021 Apr 8 TI - Whole-exome sequencing reveals the etiology of the rare primary hepatic mucoepidermoid carcinoma. PG - 29 LID - 10.1186/s13000-021-01086-3 [doi] LID - 29 AB - BACKGROUND: Primary hepatic mucoepidermoid carcinoma (HMEC) is extremely rare and the molecular etiology is still unknown. The CRTC1-MAML2 fusion gene was previously detected in a primary HMEC, which is often associated with MEC of salivary gland in the literature. METHODS: A 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 the CRTC1-MAML2 fusion 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. RESULTS: Hematoxylin-eosin staining and immunohistochemistry revealed that the tumor cells were composed of malignant epidermoid malignant cells and mucous cells, indicating a diagnosis of HMEC. The CRTC1-MAML2 fusion gene was not detected in the primary HMEC, and somatic mutations in GNAS, KMT2C and ELF3 genes were identified by sequencing. Analyses of public data revealed somatic GNAS alterations in 2.1% hepatobiliary tumors and relation with parasite infection. Heterozygous germline mutations of FANCA, FANCI, FANCJ/BRIP1 and FAN1 genes were also identified. Pedigree investigation verified that mutation of Fanconi's anemia susceptibility genes were present in the pedigree. CONCLUSIONS: Here 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. FAU - Hou, Ping AU - Hou P AD - Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanchang University, No.1, Minde Road, Nanchang, China. FAU - Su, Xiaoyan AU - Su X AD - Department of Pathology, The Second Affiliated Hospital of Nanchang University, No.1, Minde Road, Nanchang, China. FAU - Cao, Wei AU - Cao W AD - Department of General Surgery, The First Affiliated Hospital of Nanchang University, No.17, Yongwaizheng Street, Nanchang, China. FAU - Xu, Liping AU - Xu L AD - Department of Pathology, The Third Affiliated Hospital of Nanchang University, No.128, Xiangshan Road, Nanchang, China. FAU - Zhang, Rongguiyi AU - Zhang R AD - Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanchang University, No.1, Minde Road, Nanchang, China. FAU - Huang, Zhihao AU - Huang Z AD - Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanchang University, No.1, Minde Road, Nanchang, China. FAU - Wang, Jiakun AU - Wang J AD - Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanchang University, No.1, Minde Road, Nanchang, China. FAU - Li, Lixiang AU - Li L AD - Department of Pathology, The Second Affiliated Hospital of Nanchang University, No.1, Minde Road, Nanchang, China. FAU - Wu, Linquan AU - Wu L AD - Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanchang University, No.1, Minde Road, Nanchang, China. Wulqnc@163.com. FAU - Liao, Wenjun AU - Liao W AD - Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanchang University, No.1, Minde Road, Nanchang, China. liaowenjun120@163.com. LA - eng GR - N0.81860431/National Natural Science Foundation of China/ GR - N0.82060447/National Natural Science Foundation of China/ GR - NO.20181BBG70025/Natural Science Foundation of Jiangxi Province/ PT - Case Reports DEP - 20210408 PL - England TA - Diagn Pathol JT - Diagnostic pathology JID - 101251558 RN - 0 (Biomarkers, Tumor) RN - 0 (Chromogranins) RN - 0 (FANCA protein, human) RN - 0 (FANCI protein, human) RN - 0 (Fanconi Anemia Complementation Group A Protein) RN - 0 (Fanconi Anemia Complementation Group Proteins) RN - 0 (Multifunctional Enzymes) RN - EC 3.1.- (Endodeoxyribonucleases) RN - EC 3.1.- (Exodeoxyribonucleases) RN - EC 3.1.- (FAN1 protein, human) RN - EC 3.6.1.- (GNAS protein, human) RN - EC 3.6.4.13 (BRIP1 protein, human) RN - EC 3.6.4.13 (RNA Helicases) RN - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs) SB - IM MH - Biomarkers, Tumor/*genetics MH - Carcinoma, Mucoepidermoid/diagnostic imaging/*genetics/pathology/surgery MH - Chromogranins/genetics MH - *DNA Mutational Analysis MH - Endodeoxyribonucleases/genetics MH - Exodeoxyribonucleases/genetics MH - Fanconi Anemia Complementation Group A Protein/genetics MH - Fanconi Anemia Complementation Group Proteins/genetics MH - GTP-Binding Protein alpha Subunits, Gs/genetics MH - *Germ-Line Mutation MH - Humans MH - Liver Neoplasms/diagnostic imaging/*genetics/pathology/surgery MH - Male MH - Middle Aged MH - Multifunctional Enzymes/genetics MH - Predictive Value of Tests MH - RNA Helicases/genetics MH - *Exome Sequencing PMC - PMC8034126 OTO - NOTNLM OT - Germline Fanconi's anemia mutation OT - Hepatic mucoepidermoid carcinoma (HMEC) OT - Somatic GNAS R201 mutation OT - Whole exome-sequencing (WES) COIS- The authors declare no conflict of interests. The authors declare no competing financial interest. EDAT- 2021/04/10 06:00 MHDA- 2021/11/18 06:00 PMCR- 2021/04/08 CRDT- 2021/04/09 05:33 PHST- 2020/10/22 00:00 [received] PHST- 2021/03/08 00:00 [accepted] PHST- 2021/04/09 05:33 [entrez] PHST- 2021/04/10 06:00 [pubmed] PHST- 2021/11/18 06:00 [medline] PHST- 2021/04/08 00:00 [pmc-release] AID - 10.1186/s13000-021-01086-3 [pii] AID - 1086 [pii] AID - 10.1186/s13000-021-01086-3 [doi] PST - epublish SO - Diagn Pathol. 2021 Apr 8;16(1):29. doi: 10.1186/s13000-021-01086-3.