Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Tao, Yang, Yang, Feng, Huayi, Cui, Bo, Lv, Zheng, Zhao, Wenlei, Zhang, Xiangyi, Ma, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
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
_version_ 1784719718451511296
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
work_keys_str_mv AT wangtao concurrentgermlineandsomaticmutationsinflcnandpreliminaryexplorationofitsfunctionacasereport
AT yangyang concurrentgermlineandsomaticmutationsinflcnandpreliminaryexplorationofitsfunctionacasereport
AT fenghuayi concurrentgermlineandsomaticmutationsinflcnandpreliminaryexplorationofitsfunctionacasereport
AT cuibo concurrentgermlineandsomaticmutationsinflcnandpreliminaryexplorationofitsfunctionacasereport
AT lvzheng concurrentgermlineandsomaticmutationsinflcnandpreliminaryexplorationofitsfunctionacasereport
AT zhaowenlei concurrentgermlineandsomaticmutationsinflcnandpreliminaryexplorationofitsfunctionacasereport
AT zhangxiangyi concurrentgermlineandsomaticmutationsinflcnandpreliminaryexplorationofitsfunctionacasereport
AT maxin concurrentgermlineandsomaticmutationsinflcnandpreliminaryexplorationofitsfunctionacasereport