The investigation for potential modifier genes in patients with neurofibromatosis type 1 based on next-generation sequencing

Autor:	Jun Chen, Hongyu Liu, Xuebing Li, Song Xu, Renwang Liu, Qinghua Zhou, Fan Yang, Tao Shi, Gang Chen, Xiongfei Li
Rok vydání:	2018
Předmět:	plexiform 0301 basic medicine Proband congenital hereditary and neonatal diseases and abnormalities Biology Gene mutation medicine.disease_cause OncoTargets and Therapy 03 medical and health sciences 0302 clinical medicine Germline mutation Plexiform neurofibroma medicine Neurofibroma Pharmacology (medical) MEN1 Neurofibromatosis Original Research Genetics modifier gene Mutation medicine.disease 030104 developmental biology Oncology 030220 oncology & carcinogenesis next-generation sequencing neurofibroma type 1 mutation
Zdroj:	OncoTargets and therapy
ISSN:	1178-6930
DOI:	10.2147/ott.s156998
Popis:	Fan Yang,1,2,* Song Xu,1,2,* Renwang Liu,1,2 Tao Shi,3 Xiongfei Li,1 Xuebing Li,2 Gang Chen,1 Hongyu Liu,2 Qinghua Zhou,1,2 Jun Chen1,2 1Department of Lung Cancer Surgery, 2Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, 3Department of Pathology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China *These authors contributed equally to this work Introduction: Neurofibromatosis type 1 (NF1) is a common Mendelian multi-system disorder that is characterized by café-au-lait spots (CLS), axillary freckling, optic glioma and plexiform neurofibroma. Various mutations of the NF1 gene are widely accepted to be the main cause of this disease, while whether there are still certain other modifier genes that could influence the phenotypes of NF1 is our concern. Patients and Methods: One proband and his father are involved, who are characterized by plexiform neurofibroma and cutaneous neurofibroma, respectively. Enhanced Computed tomography (CT) and Positron emission tomography-CT (PET-CT) were taken to collect the radiographic data, and the specimens of this neurofibroma as well as the blood samples from the father and son were sent for panel mutation screening of 295 tumor-related genes based on next-generation screening. Furthermore, the NF1 gene mutations were referred with Canis lupus familiaris, Rattus norvegicus, Gallus gallus, Danio rerio, and Drosophila melanogaster NF1 sequencing for evolutionary conservativeness and then analyzed in Condel databases for pathogenicity prediction. Results: The radiography indicated that the benign plexiform neurofibroma only occurred in the son. Also, TP53, FANCA, BCL6, PIK3C2G, RNF43, FGFR4, FLT3, ERBB2, PAK7, NSD1, MEN1 and TSC1 were uniquely found mutated in the son, which could be candidates as new modifier genes; besides, RNF43 was also mutated in public neurofibroma seuquencing data. By KEGG pathway annotation, phosphoinositide-3-kinase-Akt pathway was altered in both the public plexiform neurofibroma sample and in our proband patient. Conclusion: This study reexamined the background germline mutations and suggested their potential value as modifier genes that may influence the phenotype heterogenity. Keywords: plexiform, neurofibroma type 1, mutation, modifier gene, next-generation sequencing
Databáze:	OpenAIRE
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