Contribution of de novo and mosaic TP53 mutations to Li-Fraumeni syndrome

Journal of Medical Genetics
Mariette Renaux-PetelGaëlle Bougeard

Abstract

Development of tumours such as adrenocortical carcinomas (ACC), choroid plexus tumours (CPT) or female breast cancers before age 31 or multiple primary cancers belonging to the Li-Fraumeni (LFS) spectrum is, independently of the familial history, highly suggestive of a germline TP53 mutation. The aim of this study was to determine the contribution of de novo and mosaic mutations to LFS. Among 328 unrelated patients harbouring a germline TP53 mutation identified by Sanger sequencing and/or QMPSF, we could show that the mutations had occurred de novo in 40 cases, without detectable parental age effect. Sanger sequencing revealed two mosaic mutations in a child with ACC and in an unaffected father of a child with medulloblastoma. Re-analysis of blood DNA by next-generation sequencing, performed at a depth above 500X, from 108 patients suggestive of LFS without detectable TP53 mutations, allowed us to identify 6 additional cases of mosaic TP53 mutations, in 2/49 children with ACC, 2/21 children with CPT, in 1/31 women with breast cancer before age 31 and in a patient who developed an osteosarcoma at age 12, a breast carcinoma and a breast sarcoma at age 35. This study performed on a large series of TP53 mutation carriers allows est...Continue Reading

References

Oct 1, 1969·Annals of Internal Medicine·F P Li, J F Fraumeni
Dec 1, 1994·Human Molecular Genetics·M I GutiérrezI T Magrath
Nov 16, 1994·Journal of the National Cancer Institute·J WagnerD Malkin
Sep 16, 1999·American Journal of Human Genetics·J M VarleyJ M Birch
Jun 23, 2000·British Journal of Cancer·A ChompretJ Feunteun
May 19, 2001·Journal of Medical Genetics·A ChompretC Bonaïti-Pellié
Apr 10, 2004·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Francisco F NogalesJosé Aneiros
Sep 24, 2004·Cancer Genetics and Cytogenetics·Ines BendigBernhard H F Weber
Jun 19, 2007·Clinical Oncology : a Journal of the Royal College of Radiologists·A SalmonT Peretz
May 31, 2008·Journal of Medical Genetics·G BougeardUNKNOWN French LFS working group
Nov 18, 2008·American Journal of Medical Genetics. Part a·Kamila ProchazkovaZdenek Sedlacek
Feb 11, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Kelly D GonzalezJeffrey N Weitzel
May 27, 2009·Familial Cancer·Carla PintoManuel R Teixeira
Jun 27, 2009·Journal of Medical Genetics·K D GonzalezS S Sommer
Aug 5, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Julie TinatThierry Frébourg
Aug 28, 2009·Pediatric Blood & Cancer·Matthew J SchniederjanAnna J Janss
Jan 12, 2012·Clinical Genetics·S S ChoongUNKNOWN Malaysian Society of Paediatric Haematology-Oncology
Jan 3, 2014·Cancer·Simone HettmerDavid Malkin
Jun 5, 2014·Nature·Christian GilissenJoris A Veltman
Jan 15, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jonathan D WassermanDavid Malkin
Mar 20, 2015·Pediatric Blood & Cancer·Brigitte SchlegelbergerMeinolf Suttorp
May 28, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Gaëlle BougeardThierry Frebourg
Oct 21, 2015·Molecular Genetics and Genomics : MGG·Marzena Gajecka
Nov 19, 2015·The New England Journal of Medicine·Jinghui ZhangJames R Downing
Dec 15, 2015·Nature Genetics·Raheleh RahbariMatthew E Hurles
Feb 6, 2016·JAMA Oncology·Elizabeth M SwisherMichael J Birrer
Mar 6, 2016·The Journal of Molecular Diagnostics : JMD·Lan QinLee-Jun C Wong
Jun 21, 2016·Nature Genetics·Jakob M GoldmannJohn E Niederhuber
Mar 3, 2017·Nature Reviews. Clinical Oncology·Giulia SiravegnaAlberto Bardelli
May 17, 2017·Familial Cancer·R O'SheaD J Gallagher
Jun 3, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christian P KratzDavid Malkin

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Citations

Mar 7, 2019·Human Mutation·Cristina FortunoPaul A James
Jul 14, 2020·Pediatric Blood & Cancer·Morgane PondromLaurence Brugières
Mar 29, 2020·European Journal of Human Genetics : EJHG·Ryota ShiraiMotohiro Kato
Sep 13, 2019·Der Pathologe·C M DutzmannB B Dörgeloh
May 28, 2020·European Journal of Human Genetics : EJHG·Thierry FrebourgUNKNOWN European Reference Network GENTURIS
Dec 5, 2019·Acta Neuropathologica Communications·Alice GoldenbergThierry Frebourg
Sep 15, 2020·JCO Precision Oncology·Lauren N DonovanLuke Maese
Jan 13, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Suzanne P MacFarland, Kara N Maxwell
May 30, 2020·Familial Cancer·Pia AlhopuroMinna Pöyhönen
Sep 10, 2020·Cancers·Jacopo AzzolliniSiranoush Manoukian
Jul 14, 2018·Journal of Adolescent and Young Adult Oncology·Rowan Forbes ShepherdLaura E Forrest
Oct 12, 2018·Oncogene·Michaela KuhlenArndt Borkhardt
Feb 2, 2019·Journal of Genetic Counseling·Martha H ThomasPatrick M Dillon
Dec 16, 2020·European Journal of Human Genetics : EJHG·Diana Le DucJohannes R Lemke
Jul 22, 2020·Cancer Discovery·Michele CarboneGiovanni Gaudino
Dec 28, 2019·The Journal of Molecular Diagnostics : JMD·Jessica L MesterKathleen S Hruska
Dec 12, 2020·Journal of Medical Ethics·Sapna Mehta, Dennis John Kuo
Dec 18, 2020·Cancers·D Gareth EvansThierry Frebourg
Mar 2, 2019·The Breast : Official Journal of the European Society of Mastology·Chrystelle ColasDominique Stoppa-Lyonnet
May 12, 2021·The Annals of Otology, Rhinology, and Laryngology·Kenny D RodriguezBrian W Herrmann
Jun 2, 2021·Familial Cancer·Anna ByrjalsenMarjolijn Jongmans
Jul 21, 2021·NPJ Genomic Medicine·Nika MaaniRaymond H Kim
Jul 10, 2021·Journal of the National Cancer Institute·Ozge Ceyhan-BirsoyDiana Mandelker
Sep 15, 2021·Familial Cancer·Elise Pierre-NoëlCaroline Abadie
Jan 20, 2022·Briefings in Bioinformatics·Gil Ben-CohenShai Rosenberg
Oct 23, 2021·Molecular Cancer Research : MCR·Emilia M PintoGerard P Zambetti

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