Loss of IDH1 and IDH2 mutations during the evolution of metastatic chondrosarcoma
Driver mutations in IDH1 and IDH2 are initiating events in the evolution of chondrosarcoma and several other cancer types. Here, we present evidence that mutant IDH1 is recurrently lost in metastatic central chondrosarcoma. This may reflect either relaxed positive selection for the mutant IDH1 locus, or negative selection for the hypermethylation phenotype later in tumor evolution. This finding highlights the challenge for therapeutic intervention by mutant IDH1 inhibitors in chondrosarcoma.
Authors
- Anna Paterson (ORCID: https://orcid.org/0000-0002-1494-0875)
- Iben Lyskjær (ORCID: https://orcid.org/0000-0003-3446-1182)
- Peter Colloby
- Cristina Naceur‐Lombardelli (ORCID: https://orcid.org/0000-0002-7097-0307)
- Teresa Marafioti (ORCID: https://orcid.org/0000-0003-1223-6275)
- Lauren Au (ORCID: https://orcid.org/0000-0001-6872-0969)
- Jennifer Biano (ORCID: https://orcid.org/0009-0000-5492-9681)
- Krijn Kristian Dijkstra (ORCID: https://orcid.org/0000-0002-5417-5397)
- Ana Ortega-Franco (ORCID: https://orcid.org/0000-0002-2865-1855)
- Claudia Lee (ORCID: https://orcid.org/0000-0003-1715-2265)
- Steve Hazell
- Benjamin Shum (ORCID: https://orcid.org/0000-0003-4397-5580)
- Irene Lobón (ORCID: https://orcid.org/0000-0003-1170-9915)
- Eleanor Carlyle (ORCID: https://orcid.org/0000-0003-3619-0742)
- Caroline Stirling
- Sebastian Brandner (ORCID: https://orcid.org/0000-0002-9821-0342)
- Kim Edmonds (ORCID: https://orcid.org/0009-0006-1910-9518)
- Deborah Enting (ORCID: https://orcid.org/0000-0001-7508-7540)
- Stefano Lise (ORCID: https://orcid.org/0000-0003-4472-6893)
- Wing-Kin Liu
- Peter Cockcroft (ORCID: https://orcid.org/0000-0003-0090-0706)
- Sophia Wong (ORCID: https://orcid.org/0000-0003-0655-3872)
- Daqi Deng (ORCID: https://orcid.org/0000-0003-0952-5455)
- Seng Kuong Anakin Ung (ORCID: https://orcid.org/0009-0007-7231-0461)
- G. Attard
- Anuradha Jayaram (ORCID: https://orcid.org/0000-0002-5255-8909)
- Corentin Richard (ORCID: https://orcid.org/0000-0001-9732-0219)
- Lavinia Spain (ORCID: https://orcid.org/0000-0002-9356-8812)
- Andreas M. Schmitt (ORCID: https://orcid.org/0000-0002-9568-8164)
- Andrew Robinson (ORCID: https://orcid.org/0000-0003-1127-6646)
- Sergio A. Quezada (ORCID: https://orcid.org/0000-0002-9763-1700)
- Ian Tomlinson
- Alex Coulton
- Kevin Litchfield (ORCID: https://orcid.org/0000-0002-3725-0914)
- William Hill (ORCID: https://orcid.org/0000-0002-9591-1389)
- Lena Karapagniotou
- Tom Watkins
- Babu Naidu
- Jayant K. Rane (ORCID: https://orcid.org/0000-0002-9594-3938)
- Nischalan Pillay (ORCID: https://orcid.org/0000-0003-0579-4105)
- Simone Zaccaria (ORCID: https://orcid.org/0000-0002-5265-7392)
- Osvaldas Vainauskas (ORCID: https://orcid.org/0009-0005-2060-7007)
- Analyn Lucanas
- Charles Swanton (ORCID: https://orcid.org/0000-0002-4299-3018)
- Takahiro Karasaki (ORCID: https://orcid.org/0000-0001-6863-2360)
- Stephan Beck (ORCID: https://orcid.org/0000-0001-5290-2151)
- Anna Wingate (ORCID: https://orcid.org/0009-0008-4965-7093)
- Allan Hackshaw (ORCID: https://orcid.org/0000-0002-5570-5070)
- Paulina Prymas
- Katey S.S. Enfield (ORCID: https://orcid.org/0000-0002-4551-6073)
- James R. Black (ORCID: https://orcid.org/0000-0001-5598-7752)
- Sophia Ward (ORCID: https://orcid.org/0000-0002-4273-9810)
- Andew Rowan
- Ursula McGovern (ORCID: https://orcid.org/0000-0001-9412-4028)
- Abby Sharp
- Foteini Athanasopoulou
- Jie Min Lam (ORCID: https://orcid.org/0000-0001-9523-5029)
- Olivia Lucas (ORCID: https://orcid.org/0000-0001-8169-7767)
- Kayleigh Kelly (ORCID: https://orcid.org/0009-0005-1285-2029)
- Haixi Yan (ORCID: https://orcid.org/0000-0002-5420-4362)
- Rodelaine Wilson
- Siow Ming Lee (ORCID: https://orcid.org/0000-0002-1741-6235)
- Blanca Trujillo Alba
- Oriol Pich (ORCID: https://orcid.org/0000-0002-1956-1882)
- Peter Hill (ORCID: https://orcid.org/0000-0002-7449-4897)
- Fábio Gomes (ORCID: https://orcid.org/0000-0003-0922-2665)
- Lisa M. Pickering (ORCID: https://orcid.org/0000-0002-7579-340X)
- Brian Hanley (ORCID: https://orcid.org/0000-0001-7940-1904)
- Vittorio Barbè
- Adrian Tookman (ORCID: https://orcid.org/0000-0003-4226-5595)
- Annika Fendler (ORCID: https://orcid.org/0000-0002-7267-0981)
- Geoffrey Hugang Feng
- David R. Pearce (ORCID: https://orcid.org/0000-0001-8443-2924)
- Nadia Yousaf (ORCID: https://orcid.org/0000-0003-2090-0025)
- Mark David Linch (ORCID: https://orcid.org/0000-0003-2305-8486)
- Jérôme Nicod (ORCID: https://orcid.org/0000-0003-2459-3480)
- Sioban Fraser
- William Cross (ORCID: https://orcid.org/0000-0001-9276-3053)
- Martin Collard
- Roberto Vendramin (ORCID: https://orcid.org/0000-0001-7191-4887)
- Claudia Peinador Marin (ORCID: https://orcid.org/0009-0003-9791-1176)
- Sarah Benafif (ORCID: https://orcid.org/0000-0003-1407-1697)
- Emma Nye (ORCID: https://orcid.org/0000-0001-9154-3526)
- Jo Dransfield
- James Spicer (ORCID: https://orcid.org/0000-0003-3732-8491)
- Sanjay Jogai
- Sonya Hessey (ORCID: https://orcid.org/0000-0001-9856-424X)
- Crispin T. Hiley (ORCID: https://orcid.org/0000-0002-5869-0775)
- Alexander M. Frankell (ORCID: https://orcid.org/0000-0002-0341-7878)
- Tânia Rita Moreno de Oliveira Fernandes (ORCID: https://orcid.org/0000-0002-7061-2825)
- Abigail Bunkum (ORCID: https://orcid.org/0000-0002-7753-9421)
- Gordon Stamp (ORCID: https://orcid.org/0000-0003-2888-4314)
- Melek Akay (ORCID: https://orcid.org/0000-0001-6093-556X)
- Paddy Stone
- Gary Middleton (ORCID: https://orcid.org/0000-0001-5695-3474)
- C. Donovan Bailey (ORCID: https://orcid.org/0000-0002-3123-4083)
- Benny Chain (ORCID: https://orcid.org/0000-0002-7417-3970)
- Mary Falzon (ORCID: https://orcid.org/0009-0006-6210-4376)
- Caroline Dive (ORCID: https://orcid.org/0000-0002-1726-8850)
- Kema Peat (ORCID: https://orcid.org/0009-0000-6063-6498)
- Arash Latifoltojar (ORCID: https://orcid.org/0000-0002-5143-746X)
- Samra Turajlic (ORCID: https://orcid.org/0000-0001-8846-136X)
- Zoe Rhodes
- Alastair Magness
- Robert E. Hynds (ORCID: https://orcid.org/0000-0002-2170-8791)
- Debra H. Josephs (ORCID: https://orcid.org/0000-0002-5610-9123)
- Teerapon Sahwangarrom
- Emma Colliver (ORCID: https://orcid.org/0000-0002-1497-0740)
- Fernanda Amary (ORCID: https://orcid.org/0000-0002-6707-8246)
- Chi-wah Lok
- Gianmarco Leone (ORCID: https://orcid.org/0000-0001-6481-0115)
- Merche Jimenez-Linan
- Clare Puttick (ORCID: https://orcid.org/0009-0006-3022-8737)
- Supreet Kaur Bola (ORCID: https://orcid.org/0000-0001-8558-8197)
- Hayley Bridger
- Olivia Curtis (ORCID: https://orcid.org/0000-0002-1509-7023)
- Ana Maia Rocha
- Thomas B.K. Watkins (ORCID: https://orcid.org/0000-0001-7414-737X)
- David Moore (ORCID: https://orcid.org/0000-0002-4163-4080)
- Christina Messiou (ORCID: https://orcid.org/0000-0002-0557-9379)
- Sanjay Popat (ORCID: https://orcid.org/0000-0003-2087-4963)
- Dhruva Biswas (ORCID: https://orcid.org/0000-0001-9141-5188)
- Husayn Pallinkonda
- Kate Young
- Mihaela Angelova (ORCID: https://orcid.org/0000-0002-0495-9695)
- Yvonne Summers
- Blanche Hampton
- Mariam Jamal‐Hanjani (ORCID: https://orcid.org/0000-0003-1212-1259)
- Alison D. Cluroe
- Camille L. Gérard (ORCID: https://orcid.org/0000-0002-6007-1746)
- Rija Zaidi (ORCID: https://orcid.org/0000-0002-2259-4319)
- Rebecca C. Fitzgerald (ORCID: https://orcid.org/0000-0002-3434-3568)
- Gerald Langman
- Dionysis Papadatos-Pastos
- James D. Brenton (ORCID: https://orcid.org/0000-0002-5738-6683)
- Patricia Roxburgh (ORCID: https://orcid.org/0000-0001-9869-591X)
- Anna Green (ORCID: https://orcid.org/0000-0002-1241-4230)
- Constantine Alifrangis (ORCID: https://orcid.org/0000-0002-5876-6696)
- Kerstin Thol (ORCID: https://orcid.org/0000-0002-4624-118X)
- Bruce Tanchel
- Selvaraju Veeriah (ORCID: https://orcid.org/0000-0002-1217-0387)
- Laura Farrelly (ORCID: https://orcid.org/0000-0002-0039-6709)
- Nicholas McGranahan (ORCID: https://orcid.org/0000-0001-9537-4045)
- John Le Quesne (ORCID: https://orcid.org/0000-0003-3552-7446)
- Molly O’Flaherty (ORCID: https://orcid.org/0009-0006-4015-839X)
- Kristiana Grigoriadis (ORCID: https://orcid.org/0000-0002-8435-0176)
- Joanne Webb (ORCID: https://orcid.org/0000-0001-6996-9897)
- Neil Magno
- Tariq Enver (ORCID: https://orcid.org/0000-0002-0866-6443)
- Christopher Davies (ORCID: https://orcid.org/0000-0002-4942-9540)
- Grant S. Stewart (ORCID: https://orcid.org/0000-0002-0960-3241)
- Antonia Toncheva
- Samuel Gamble
- Carlos Martínez‐Ruiz (ORCID: https://orcid.org/0000-0002-4817-0565)
- Fiona Byrne (ORCID: https://orcid.org/0000-0003-3800-0500)
- Nikki Hunter (ORCID: https://orcid.org/0009-0006-0825-3821)
- Faye Gishen (ORCID: https://orcid.org/0000-0003-2603-2759)
- Sam M. Janes (ORCID: https://orcid.org/0000-0002-6634-5939)
- Charlotte Ferris (ORCID: https://orcid.org/0000-0003-1164-8841)
- Jacqui Shaw (ORCID: https://orcid.org/0000-0003-4227-503X)
- Sarah J. Aitken (ORCID: https://orcid.org/0000-0002-1897-4140)
- Lauren Terry (ORCID: https://orcid.org/0009-0001-5060-7279)
- Kieren Allinson (ORCID: https://orcid.org/0000-0003-3468-2110)
- Max Emmerich (ORCID: https://orcid.org/0000-0002-2026-974X)
- Michelle Dietzen (ORCID: https://orcid.org/0000-0002-6853-7563)
- Anne Laure Cattin
- Samantha K. Holden (ORCID: https://orcid.org/0000-0001-6494-0606)
- Elena Provenzano (ORCID: https://orcid.org/0000-0003-3345-3965)
- Karla Pearce
- Miriam Mitchison (ORCID: https://orcid.org/0000-0003-2520-2744)
- Charlotte Milner-Watts (ORCID: https://orcid.org/0000-0001-7826-2754)
- Sarah Howlett
- Roberto Tirabosco (ORCID: https://orcid.org/0000-0003-0671-7531)
- Ariana Huebner
- James Larkin (ORCID: https://orcid.org/0000-0001-5569-9523)
- Rachel Leslie
- Maise Al-Bakir
- Ruby M. Stewart
- Martin Förster (ORCID: https://orcid.org/0000-0003-3876-7269)
- Imran Noorani (ORCID: https://orcid.org/0000-0003-4289-2345)
- Ultan McDermott (ORCID: https://orcid.org/0000-0001-9032-4700)
- Scott T.C. Shepherd (ORCID: https://orcid.org/0000-0001-6208-173X)
- Matthew Krebs (ORCID: https://orcid.org/0000-0001-7540-3064)
- Hardeep Singh Mudhar (ORCID: https://orcid.org/0000-0002-9915-2594)
- Will Drake
- Kitty S. Chan (ORCID: https://orcid.org/0000-0003-2639-4186)
- Charlotte Spencer (ORCID: https://orcid.org/0000-0003-1339-9922)
- Mairead McKenzie
- Sheeba Irshad (ORCID: https://orcid.org/0000-0002-4419-7162)
- Daniel Hochhauser (ORCID: https://orcid.org/0000-0001-5522-9281)
- Justine Korteweg (ORCID: https://orcid.org/0009-0002-4665-0968)
- Othman Al‐Sawaf (ORCID: https://orcid.org/0000-0001-9895-0570)
- Ron Sinclair
- Olaf Ansorge (ORCID: https://orcid.org/0000-0003-1825-5434)
- Andrew N.J. Tutt (ORCID: https://orcid.org/0000-0001-8715-2901)
- Ula Mahadeva (ORCID: https://orcid.org/0000-0002-9459-3403)
- Daniel Wetterskog (ORCID: https://orcid.org/0000-0003-4163-6438)
- Ian Proctor (ORCID: https://orcid.org/0009-0006-3091-9124)
- Emma Beddowes (ORCID: https://orcid.org/0000-0001-7649-2863)
- Tim Maughan (ORCID: https://orcid.org/0000-0002-0580-5065)
- Carlos Caldas (ORCID: https://orcid.org/0000-0003-3547-1489)
- Iain A. McNeish (ORCID: https://orcid.org/0000-0002-9387-7586)
- Fiona Helen Blackhall (ORCID: https://orcid.org/0000-0001-8716-3395)
- James L. Reading (ORCID: https://orcid.org/0000-0001-5381-978X)
- Aida Murra (ORCID: https://orcid.org/0009-0007-9524-7995)
- Bernard Olisemeke
- Georgina Pulman
- Ruxandra Mitu
- Sherene Phillips-Boyd
- Pedro Oliveira (ORCID: https://orcid.org/0000-0001-8912-2490)
- Mahedi Hasan (ORCID: https://orcid.org/0000-0002-9309-344X)
- Shobhit Baijal (ORCID: https://orcid.org/0000-0002-5842-6886)
- Piotr Pawlik (ORCID: https://orcid.org/0009-0008-7075-615X)
- Heather M. Shaw (ORCID: https://orcid.org/0000-0002-6545-2927)
- Anne Thomas (ORCID: https://orcid.org/0000-0001-6901-3844)
- Elias Pintus (ORCID: https://orcid.org/0000-0001-5123-1835)
- D. F. Kelly
- Charlotte Lewis (ORCID: https://orcid.org/0000-0003-0918-9201)
- Natasha Wright
- Peter Ellery
- Peter J. Campbell
- Kai‐Keen Shiu
- Peter Van Loo
- Mat Carter
- Tanya Ahmad
- Zayd Tippu
- Salma Kadiri
- Monica Sivakumar
- Dean Fennell
- Sarah Rudman (ORCID: https://orcid.org/0000-0001-9447-8985)
- Sharmistha Ghosh
- Lucy Holt
- Adrienne M. Flanagan
- Hollie Bancroft
- Andrew Furness
- Mary Mangwende
- Lyra Del Rosario
- Kevin Blyth
- Roberto Salgado
- Andrew Rowan
- Emilia L. Lim (ORCID: https://orcid.org/0009-0009-2954-1795)
- Amy Kerr
- John Bridgewater
- Tom Lesluyes
- Nnenna Kanu
Institutions
- The University of Texas MD Anderson Cancer Center (US)
- The Francis Crick Institute (GB)
- Royal London Hospital (GB)
- Cancer Research UK (GB)
- Aarhus University Hospital (DK)
- Royal National Orthopaedic Hospital (GB)
- CRUK Lung Cancer Centre of Excellence (GB)
- Genomics (United Kingdom) (GB)
- University College London (GB)
- University of Reading (GB)
Publication Details
- Journal
- Genome biology
- Published
- 2025-11-26
- DOI
- https://doi.org/10.1186/s13059-025-03812-2
- Primary Topic
- Bone Tumor Diagnosis and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- American Association for Cancer Research
- Breast Cancer Research Foundation
- LUNGevity Foundation
- Cancer Prevention and Research Institute of Texas
- International Association for the Study of Lung Cancer
- Sarcoma UK
- Wellcome Trust
- Francis Crick Institute
- Mark Foundation For Cancer Research
- Cancer Research UK
- National Institute for Health and Care Research
- University College London
- European Commission
- Rosetrees Trust
- Lundbeckfonden
- University College London Hospitals NHS Foundation Trust
- H. Lundbeck A/S
- Stand Up To Cancer
- Medical Research Council