Response to everolimus is seen in TSC-associated SEGAs and angiomyolipomas independent of mutation type and site in TSC1 and TSC2

European Journal of Human Genetics : EJHG
David KwiatkowskiJulian Sampson

Abstract

Tuberous sclerosis complex is an autosomal dominant disorder that occurs owing to inactivating mutations in either TSC1 or TSC2. Tuberous sclerosis complex-related tumors in the brain, such as subependymal giant cell astrocytoma, and in the kidney, such as angiomyolipoma, can cause significant morbidity and mortality. Recently, randomized clinical trials (EXIST-1 and EXIST-2) of everolimus for each of these tuberous sclerosis complex-associated tumors demonstrated the benefit of this drug, which blocks activated mammalian target of rapamycin complex 1. Here we report on the spectrum of mutations seen in patients treated during these trials and the association between mutation and response. TSC2 mutations were predominant among patients in both trials and were present in nearly all subjects with angiomyolipoma in whom a mutation was identified (97%), whereas TSC1 mutations were rare in those subjects (3%). The spectrum of mutations seen in each gene was similar to those previously reported. In both trials, there was no apparent association between mutation type or location within each gene and response to everolimus. Everolimus responses were also seen at a similar frequency for the 16-18% of patients in each trial in whom no mu...Continue Reading

References

Nov 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·S Henikoff, J G Henikoff
Oct 23, 1997·American Journal of Human Genetics·J R SampsonP C Harris
Apr 16, 1998·American Journal of Human Genetics·K S AuH Northrup
Mar 4, 1999·The New England Journal of Medicine·J KwiatkowskaD J Kwiatkowski
Feb 3, 2006·Annals of Neurology·David Neal FranzKerry R Crone
Mar 24, 2006·Brain & Development·Ji-Eun ChoiKi-Joong Kim
Sep 20, 2006·BMC Medical Genetics·Chia-Cheng HungChien-Nan Lee
Nov 23, 2006·Annals of Neurology·An C JansenEva Andermann
Feb 17, 2007·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Kit Sing AuHope Northrup
Jan 11, 2008·The New England Journal of Medicine·John J BisslerDavid N Franz
Jun 6, 2009·BJU International·Prasanna SooriakumaranChristopher Anderson
Nov 5, 2010·The New England Journal of Medicine·Darcy A KruegerDavid Neal Franz
Nov 13, 2010·Nephron. Experimental Nephrology·Bradley P DixonJohn J Bissler
Mar 18, 2011·The New England Journal of Medicine·Francis X McCormackUNKNOWN MILES Trial Group
Apr 29, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·D Mark DaviesJulian R Sampson
Jan 18, 2013·Neurology·Darcy A KruegerDavid Neal Franz
Feb 9, 2013·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Sergiusz JóźwiakUNKNOWN participants of the TSC Consensus Meeting for SEGA and Epilepsy Management
Feb 11, 2014·Pediatric Neurology·Katarzyna KotulskaSergiusz Jóźwiak

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Citations

Dec 27, 2015·Seminars in Pediatric Neurology·Paolo CuratoloFederica Graziola
Dec 27, 2015·Seminars in Pediatric Neurology·Sergiusz JóźwiakWojciech Młynarski
Sep 24, 2015·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Dritan Liko, Michael N Hall
Sep 27, 2018·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Angela PeronHope Northrup
Dec 5, 2017·Continuum : Lifelong Learning in Neurology·Roy E Strowd, Jaishri O Blakeley
Feb 25, 2018·Journal of Human Genetics·Evgeny N SuspitsinEvgeny N Imyanitov
Jul 22, 2019·Nature Communications·Katherine H SchreiberDudley W Lamming
Sep 21, 2017·Oncology Letters·Mingwei JinLei Wang
Feb 21, 2019·Nature Reviews. Clinical Oncology·Subotheni ThavaneswaranDavid M Thomas
Mar 20, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wendy ChangJaved Khan
Mar 18, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Elio AdibDavid J Kwiatkowski

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Methods Mentioned

BETA
surgical resection
deamination
PCR

Software Mentioned

GeneMarker
GraphPad
MLPA

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