NGS Uncovers New Pathogenic Mechanisms in Tuberous Sclerosis Complex Tumours
Next-generation sequencing has revealed unexpected pathogenic mechanisms in tuberous sclerosis complex, including UV-induced mutations driving angiofibromas and distinct second-hit mutations causing multifocal renal cell carcinoma. These discoveries refine the understanding of mTORC1-driven tumorigenesis in TSC and have direct implications for clinical management, which has undergone paradigm-shifting changes in recent years. The findings also continue to define new pathological features of TSC-associated renal cell carcinoma subtypes.
The original study
New developments in the genetics and pathogenesis of tumours in tuberous sclerosis complex.
- Authors
- Lam HC, Nijmeh J, Henske EP
- Journal
- The Journal of pathology
- Type
- Journal Article, Review
- PMID
- 27753446
Original 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.