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Concurrent Germline and Somatic Mutations in FLCN and Preliminary Exploration of Its Function: A Case Report
Birt–Hogg–Dube syndrome is an autosomal dominant condition that arises from germline folliculin (FLCN) mutations. It is characterized by skin fibrofolliculomas, lung cysts, pneumothorax, and renal cancer. Here, we present the case of a 36-year-old woman with asymptomatic, multiple renal tumors and a...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9162506/ https://www.ncbi.nlm.nih.gov/pubmed/35664771 http://dx.doi.org/10.3389/fonc.2022.877470 |
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author | Wang, Tao Yang, Yang Feng, Huayi Cui, Bo Lv, Zheng Zhao, Wenlei Zhang, Xiangyi Ma, Xin |
author_facet | Wang, Tao Yang, Yang Feng, Huayi Cui, Bo Lv, Zheng Zhao, Wenlei Zhang, Xiangyi Ma, Xin |
author_sort | Wang, Tao |
collection | PubMed |
description | Birt–Hogg–Dube syndrome is an autosomal dominant condition that arises from germline folliculin (FLCN) mutations. It is characterized by skin fibrofolliculomas, lung cysts, pneumothorax, and renal cancer. Here, we present the case of a 36-year-old woman with asymptomatic, multiple renal tumors and a history of spontaneous pneumothorax. Genetic analysis revealed a hotspot FLCN germline mutation, c.1285dupC (p.H429fs), and a novel somatic mutation, c.470delT (p.F157fs). This information and the results of immunohistochemical analysis of the renal tumors indicated features compatible with a tumor suppressor role of FLCN. Two transcription factors, oncogenic TFEB and TFE3, were shown to be regulated by FLCN inactivation, which results in their nuclear localization. We showed that a deficiency in the tumor suppressor FLCN leads to deregulation of the mammalian target of rapamycin signaling (mTOR) pathway. A potential link between FLCN mutation and ciliary length was also examined. Thus, the mutation identified in our patient provides novel insights into the relationship among FLCN mutations, TFEB/TFE3, mTOR, and cilia. However, an in-depth understanding of the role of folliculin in the molecular pathogenesis of renal cancer requires further study. |
format | Online Article Text |
id | pubmed-9162506 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91625062022-06-03 Concurrent Germline and Somatic Mutations in FLCN and Preliminary Exploration of Its Function: A Case Report Wang, Tao Yang, Yang Feng, Huayi Cui, Bo Lv, Zheng Zhao, Wenlei Zhang, Xiangyi Ma, Xin Front Oncol Oncology Birt–Hogg–Dube syndrome is an autosomal dominant condition that arises from germline folliculin (FLCN) mutations. It is characterized by skin fibrofolliculomas, lung cysts, pneumothorax, and renal cancer. Here, we present the case of a 36-year-old woman with asymptomatic, multiple renal tumors and a history of spontaneous pneumothorax. Genetic analysis revealed a hotspot FLCN germline mutation, c.1285dupC (p.H429fs), and a novel somatic mutation, c.470delT (p.F157fs). This information and the results of immunohistochemical analysis of the renal tumors indicated features compatible with a tumor suppressor role of FLCN. Two transcription factors, oncogenic TFEB and TFE3, were shown to be regulated by FLCN inactivation, which results in their nuclear localization. We showed that a deficiency in the tumor suppressor FLCN leads to deregulation of the mammalian target of rapamycin signaling (mTOR) pathway. A potential link between FLCN mutation and ciliary length was also examined. Thus, the mutation identified in our patient provides novel insights into the relationship among FLCN mutations, TFEB/TFE3, mTOR, and cilia. However, an in-depth understanding of the role of folliculin in the molecular pathogenesis of renal cancer requires further study. Frontiers Media S.A. 2022-05-19 /pmc/articles/PMC9162506/ /pubmed/35664771 http://dx.doi.org/10.3389/fonc.2022.877470 Text en Copyright © 2022 Wang, Yang, Feng, Cui, Lv, Zhao, Zhang and Ma https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Wang, Tao Yang, Yang Feng, Huayi Cui, Bo Lv, Zheng Zhao, Wenlei Zhang, Xiangyi Ma, Xin Concurrent Germline and Somatic Mutations in FLCN and Preliminary Exploration of Its Function: A Case Report |
title | Concurrent Germline and Somatic Mutations in FLCN and Preliminary Exploration of Its Function: A Case Report |
title_full | Concurrent Germline and Somatic Mutations in FLCN and Preliminary Exploration of Its Function: A Case Report |
title_fullStr | Concurrent Germline and Somatic Mutations in FLCN and Preliminary Exploration of Its Function: A Case Report |
title_full_unstemmed | Concurrent Germline and Somatic Mutations in FLCN and Preliminary Exploration of Its Function: A Case Report |
title_short | Concurrent Germline and Somatic Mutations in FLCN and Preliminary Exploration of Its Function: A Case Report |
title_sort | concurrent germline and somatic mutations in flcn and preliminary exploration of its function: a case report |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9162506/ https://www.ncbi.nlm.nih.gov/pubmed/35664771 http://dx.doi.org/10.3389/fonc.2022.877470 |
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