Sporadic renal angiomyolipoma in a patient with Birt-Hogg-Dubé: chaperones in pathogenesis
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Rebecca A. Sager1,2,3, Mark R. Woodford1,2,3, Oleg Shapiro1,2, Mehdi Mollapour1,2,3 and Gennady Bratslavsky1,2
1Department of Urology, SUNY Upstate Medical University, Syracuse, NY, USA
2Upstate Cancer Center, SUNY Upstate Medical University, Syracuse, NY, USA
3Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY, USA
Mehdi Mollapour, email: email@example.com
Gennady Bratslavsky, email: firstname.lastname@example.org
Keywords: Birt-Hogg-Dubé (BHD); FLCN; tuberous sclerosis complex (TSC); renal angiomyolipoma; TSC1 (Hamartin)
Received: March 22, 2018 Accepted: April 02, 2018 Published: April 24, 2018
Birt-Hogg-Dubé (BHD) is an autosomal dominant genetic syndrome caused by germline mutations in the FLCN gene that predisposes patients to develop renal tumors. Renal angiomyolipoma (AML) is not a renal tumor sub-type associated with BHD. AML is, however, a common phenotypic manifestation of Tuberous Sclerosis Complex (TSC) syndrome caused by mutations in either the TSC1 or TSC2 tumor suppressor genes. Previous case reports of renal AML in patients with BHD have speculated on the molecular and clinical overlap of these two syndromes as a result of described involvement of the gene products in the mTOR pathway. Our recent work provided a new molecular link between these two syndromes by identifying FLCN and Tsc2 as clients of the molecular chaperone Hsp90. Folliculin interacting proteins FNIP1/2 and Tsc1 are important for FLCN and Tsc2 stability as new Hsp90 co-chaperones. Here we present a case of sporadic AML as a result of somatic Tsc1/2 loss in a patient with BHD. We further demonstrate that FNIP1 and Tsc1 are capable of compensating for each other in the chaperoning of mutated FLCN tumor suppressor. Our findings demonstrate interconnectivity and compensatory mechanisms between the BHD and TSC pathways.
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