title: New developments in the genetics and pathogenesis of tumours in tuberous sclerosis complex.
abstract: In just the past 5 years, dramatic changes have occurred in the clinical management of tuberous sclerosis complex (TSC). Detailed knowledge about the role of the TSC proteins in regulating the activity of the mammalian target of rapamycin complex 1 (mTORC1) underlies this paradigm-shifting progress. Advances continue to be made in understanding the genetic pathogenesis of the different tumours that occur in TSC, including pivotal discoveries using next-generation sequencing (NGS). For example, the pathogenesis of angiofibromas is now known to involve UV-induced mutations, and the pathogenesis of multifocal renal cell carcinoma (RCC) in TSC is now known to result from distinct second-hit mutations. In parallel, the pathological features of TSC-associated tumours, including TSC-associated renal cell carcinoma, continue to be defined, despite the fact that TSC was first described 180 years ago. Here, we review recent discoveries related to the pathological features and genetic pathogenesis of TSC-associated tumours. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
authors.affiliation: Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Hilaire C
authors.initials: HC
authors.lastname: Lam
authors.affiliation: Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Nijmeh
authors.affiliation: Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Henske
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D009154:Mutation / Q000235:genetics; D014402:Tuberous Sclerosis / Q000175:diagnosis* / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins
keywords: angiofibroma; angiomyolipoma (AML); lymphangioleiomyomatosis (LAM); mosaicism; next-generation sequencing (NGS); no mutation identified (NMI); renal cell carcinoma (RCC); tuberous sclerosis complex (TSC)