Cover Image

Germline RET variants underlie a subset of paediatric osteosarcoma

Background Although considerable effort has been put into decoding of the osteosarcoma genome, very little is known about germline mutations that underlie this primary malignant tumour of bone. - Methods and results We followed here a coincidental finding in a multiple endocrine neoplasia family in...

Full description

Saved in:
Bibliographic Details
Main Authors: Kovac, Michal (Author) , Woolley, Connor (Author) , Ribi, Sebastian (Author) , Blattmann, Claudia (Author) , Roth, Eva Kathrin (Author) , Morini, Marco (Author) , Kovacova, Monika (Author) , Ameline, Baptiste (Author) , Kulozik, Andreas (Author) , Bielack, Stefan (Author) , Hartmann, Wolfgang (Author) , Ballinger, Mandy L. (Author) , Thomas, David M. (Author) , Tomlinson, Ian (Author) , Nathrath, Michaela (Author) , Heinimann, Karl (Author) , Baumhoer, Daniel (Author)
Format: Article (Journal)
Language:English
Published: 2021
In: Journal of medical genetics
Year: 2020, Volume: 58, Issue: 1, Pages: 20-24
ISSN:1468-6244
DOI:10.1136/jmedgenet-2019-106734
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1136/jmedgenet-2019-106734
Verlag, lizenzpflichtig, Volltext: https://jmg.bmj.com/content/58/1/20
Get full text
Author Notes:Michal Kovac, Connor Woolley, Sebastian Ribi, Claudia Blattmann, Eva Roth, Marco Morini, Monika Kovacova, Baptiste Ameline, Andreas Kulozik, Stefan Bielack, Wolfgang Hartmann, Mandy L. Ballinger, David M. Thomas, Ian Tomlinson, Michaela Nathrath, Karl Heinimann, Daniel Baumhoer

MARC

LEADER 00000caa a2200000 c 4500
001 1750865297
003 DE-627
005 20230426083823.0
007 cr uuu---uuuuu
008 210309r20212020xx |||||o 00| ||eng c
024 7 |a 10.1136/jmedgenet-2019-106734  |2 doi 
035 |a (DE-627)1750865297 
035 |a (DE-599)KXP1750865297 
035 |a (OCoLC)1341398331 
040 |a DE-627  |b ger  |c DE-627  |e rda 
041 |a eng 
084 |a 33  |2 sdnb 
100 1 |a Kovac, Michal  |e VerfasserIn  |0 (DE-588)1214325815  |0 (DE-627)1725300184  |4 aut 
245 1 0 |a Germline RET variants underlie a subset of paediatric osteosarcoma  |c Michal Kovac, Connor Woolley, Sebastian Ribi, Claudia Blattmann, Eva Roth, Marco Morini, Monika Kovacova, Baptiste Ameline, Andreas Kulozik, Stefan Bielack, Wolfgang Hartmann, Mandy L. Ballinger, David M. Thomas, Ian Tomlinson, Michaela Nathrath, Karl Heinimann, Daniel Baumhoer 
264 1 |c 2021 
300 |a 5 
336 |a Text  |b txt  |2 rdacontent 
337 |a Computermedien  |b c  |2 rdamedia 
338 |a Online-Ressource  |b cr  |2 rdacarrier 
500 |a Published Online First 16 March 2020 
500 |a Gesehen am 09.03.2021 
520 |a Background Although considerable effort has been put into decoding of the osteosarcoma genome, very little is known about germline mutations that underlie this primary malignant tumour of bone. - Methods and results We followed here a coincidental finding in a multiple endocrine neoplasia family in which a 32-year-old patient carrying a germline pathogenic RET mutation developed an osteosarcoma 2 years after the resection of a medullary thyroid carcinoma. Sequencing analysis of additional 336 patients with osteosarcoma led to the identification of germline activating mutations in the RET proto-oncogene in three cases and somatic amplifications of the gene locus in five matched tumours (4%, n=5/124 tumours). Functional analysis of the pathogenic variants together with an integrative analysis of osteosarcoma genomes confirmed that the mutant RET proteins couple functional kinase activity to dysfunctional ligand binding. RET mutations further co-operated with alterations in TP53 and RB1, suggesting that osteosarcoma pathogenesis bears reminiscence to the stepwise model of medullary thyroid carcinoma. - Conclusions After Li-Fraumeni-predisposing mutations in TP53, RET becomes the second most mutated cancer-predisposing gene in the germline of patients with osteosarcoma. Hence, early identification of RET mutation carriers can help to identify at-risk family members and carry out preventive measures. 
534 |c 2020 
650 4 |a calcium and bone 
650 4 |a molecular genetics 
650 4 |a paediatric oncology 
700 1 |a Woolley, Connor  |e VerfasserIn  |4 aut 
700 1 |a Ribi, Sebastian  |e VerfasserIn  |4 aut 
700 1 |a Blattmann, Claudia  |e VerfasserIn  |0 (DE-588)1074706099  |0 (DE-627)832365963  |0 (DE-576)414107284  |4 aut 
700 1 |a Roth, Eva Kathrin  |d 1985-  |e VerfasserIn  |0 (DE-588)102540484X  |0 (DE-627)722218761  |0 (DE-576)37031218X  |4 aut 
700 1 |a Morini, Marco  |e VerfasserIn  |4 aut 
700 1 |a Kovacova, Monika  |e VerfasserIn  |4 aut 
700 1 |a Ameline, Baptiste  |e VerfasserIn  |4 aut 
700 1 |a Kulozik, Andreas  |d 1959-  |e VerfasserIn  |0 (DE-588)1025736567  |0 (DE-627)723892032  |0 (DE-576)167091638  |4 aut 
700 1 |a Bielack, Stefan  |e VerfasserIn  |4 aut 
700 1 |a Hartmann, Wolfgang  |e VerfasserIn  |4 aut 
700 1 |a Ballinger, Mandy L.  |e VerfasserIn  |4 aut 
700 1 |a Thomas, David M.  |e VerfasserIn  |4 aut 
700 1 |a Tomlinson, Ian  |e VerfasserIn  |4 aut 
700 1 |a Nathrath, Michaela  |e VerfasserIn  |4 aut 
700 1 |a Heinimann, Karl  |e VerfasserIn  |4 aut 
700 1 |a Baumhoer, Daniel  |e VerfasserIn  |4 aut 
773 0 8 |i Enthalten in  |t Journal of medical genetics  |d London : BMJ Publishing Group, 1964  |g 58(2021), 1, Seite 20-24  |h Online-Ressource  |w (DE-627)319102661  |w (DE-600)2009590-9  |w (DE-576)091210003  |x 1468-6244  |7 nnas  |a Germline RET variants underlie a subset of paediatric osteosarcoma 
773 1 8 |g volume:58  |g year:2021  |g number:1  |g pages:20-24  |g extent:5  |a Germline RET variants underlie a subset of paediatric osteosarcoma 
856 4 0 |u https://doi.org/10.1136/jmedgenet-2019-106734  |x Verlag  |x Resolving-System  |z lizenzpflichtig  |3 Volltext 
856 4 0 |u https://jmg.bmj.com/content/58/1/20  |x Verlag  |z lizenzpflichtig  |3 Volltext 
951 |a AR 
992 |a 20210309 
993 |a Article 
994 |a 2021 
998 |g 1025736567  |a Kulozik, Andreas  |m 1025736567:Kulozik, Andreas  |d 910000  |d 910500  |e 910000PK1025736567  |e 910500PK1025736567  |k 0/910000/  |k 1/910000/910500/  |p 9 
998 |g 102540484X  |a Roth, Eva Kathrin  |m 102540484X:Roth, Eva Kathrin  |d 910000  |d 910500  |e 910000PR102540484X  |e 910500PR102540484X  |k 0/910000/  |k 1/910000/910500/  |p 5 
999 |a KXP-PPN1750865297  |e 3883172960 
BIB |a Y 
SER |a journal 
JSO |a {"id":{"doi":["10.1136/jmedgenet-2019-106734"],"eki":["1750865297"]},"origin":[{"dateIssuedKey":"2021","dateIssuedDisp":"2021"}],"name":{"displayForm":["Michal Kovac, Connor Woolley, Sebastian Ribi, Claudia Blattmann, Eva Roth, Marco Morini, Monika Kovacova, Baptiste Ameline, Andreas Kulozik, Stefan Bielack, Wolfgang Hartmann, Mandy L. Ballinger, David M. Thomas, Ian Tomlinson, Michaela Nathrath, Karl Heinimann, Daniel Baumhoer"]},"recId":"1750865297","person":[{"family":"Kovac","given":"Michal","role":"aut","display":"Kovac, Michal"},{"display":"Woolley, Connor","family":"Woolley","role":"aut","given":"Connor"},{"family":"Ribi","given":"Sebastian","role":"aut","display":"Ribi, Sebastian"},{"display":"Blattmann, Claudia","family":"Blattmann","role":"aut","given":"Claudia"},{"family":"Roth","given":"Eva Kathrin","role":"aut","display":"Roth, Eva Kathrin"},{"display":"Morini, Marco","role":"aut","given":"Marco","family":"Morini"},{"display":"Kovacova, Monika","family":"Kovacova","role":"aut","given":"Monika"},{"family":"Ameline","role":"aut","given":"Baptiste","display":"Ameline, Baptiste"},{"display":"Kulozik, Andreas","family":"Kulozik","given":"Andreas","role":"aut"},{"display":"Bielack, Stefan","role":"aut","given":"Stefan","family":"Bielack"},{"given":"Wolfgang","role":"aut","family":"Hartmann","display":"Hartmann, Wolfgang"},{"display":"Ballinger, Mandy L.","given":"Mandy L.","role":"aut","family":"Ballinger"},{"role":"aut","given":"David M.","family":"Thomas","display":"Thomas, David M."},{"family":"Tomlinson","given":"Ian","role":"aut","display":"Tomlinson, Ian"},{"role":"aut","given":"Michaela","family":"Nathrath","display":"Nathrath, Michaela"},{"role":"aut","given":"Karl","family":"Heinimann","display":"Heinimann, Karl"},{"display":"Baumhoer, Daniel","family":"Baumhoer","role":"aut","given":"Daniel"}],"title":[{"title":"Germline RET variants underlie a subset of paediatric osteosarcoma","title_sort":"Germline RET variants underlie a subset of paediatric osteosarcoma"}],"physDesc":[{"extent":"5 S."}],"language":["eng"],"type":{"bibl":"article-journal","media":"Online-Ressource"},"relHost":[{"title":[{"title":"Journal of medical genetics","title_sort":"Journal of medical genetics"}],"type":{"media":"Online-Ressource","bibl":"periodical"},"titleAlt":[{"title":"JMG"},{"title":"Journal of medical genetics"}],"note":["Gesehen am 12.08.20"],"pubHistory":["1.1964 -"],"language":["eng"],"physDesc":[{"extent":"Online-Ressource"}],"id":{"zdb":["2009590-9"],"issn":["1468-6244"],"eki":["319102661"]},"origin":[{"dateIssuedDisp":"1964-","dateIssuedKey":"1964","publisher":"BMJ Publishing Group","publisherPlace":"London"}],"part":{"issue":"1","year":"2021","volume":"58","pages":"20-24","text":"58(2021), 1, Seite 20-24","extent":"5"},"recId":"319102661","disp":"Germline RET variants underlie a subset of paediatric osteosarcomaJournal of medical genetics"}],"note":["Published Online First 16 March 2020","Gesehen am 09.03.2021"]} 
SRT |a KOVACMICHAGERMLINERE2021 

Similar Items