On Folliculin: Molecular pathways and roles in Birt-Hogg-Dubé syndrome

Iris Elefteria Glykofridis, A.C. Houweling (Co-supervisor)

Research output: PhD ThesisPhd-Thesis - Research and graduation internal

Abstract

Most cancer occurs as a sporadic disease, in which gene mutations or genomics alterations that cause tumor growth are not inherited, but acquired. About 5% of all cancers have a hereditary origin, where germline mutations in a high risk gene predispose carriers to early onset of specific tumors. Birt-Hogg-Dubé syndrome (BHD, OMIM #135150) is an autosomal dominant inherited disorder, which was first described by the three physicians Arthur Birt, Georgina Hogg and James Dubé in 1977 and linked to truncating variants in the folliculin (FLCN) gene in 2002. BHD patients are predisposed to develop benign cutaneous tumors (fibrofolliculomas), pulmonary cysts, pneumothoraces and renal tumors (renal cell carcinomas). The aim of the research described in this thesis is to provide a basis for the further elucidation of how folliculin is able to act as a tissue-specific tumor suppressor. In the first part of this thesis, we describe the effects downstream of FLCN inactivation in human renal cells and how this may contribute to kidney specific tumor formation. In the second part, the focus is on investigations of BHD patients with a remarkable phenotype, and families with a BHD-associated phenotype, but without an identifiable FLCN germline variant, which provides novel insights in the regulation and function of folliculin.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Supervisors/Advisors
  • Meijers-Heijboer, Hanne, Supervisor
  • Jimenez, Connie, Supervisor
  • Wolthuis, Rob, Co-supervisor
  • Houweling, Arjan, Co-supervisor
Award date22 Nov 2022
Place of Publications.l.
Publisher
Print ISBNs9789464218749
Electronic ISBNs9789464218749
Publication statusPublished - 22 Nov 2022

Keywords

  • BHD
  • Birt-Hogg-Dubé syndrome
  • FLCN
  • Folliculin
  • OMIM #135150
  • RCC
  • RPTEC
  • renal epithelial cells
  • transcription factors

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