Loss of IDH1 and IDH2 mutations during the evolution of metastatic chondrosarcoma

PEACE Consortium

doi:10.1186/s13059-025-03812-2

Loss of IDH1 and IDH2 mutations during the evolution of metastatic chondrosarcoma

PEACE Consortium

Genetics

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

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.

Original language	English (US)
Article number	404
Journal	Genome biology
Volume	26
Issue number	1
DOIs	https://doi.org/10.1186/s13059-025-03812-2
State	Published - Dec 2025

Keywords

Bone tumor
Cancer evolution
Chondrosarcoma
IDH1
IDH2
Metastasis

ASJC Scopus subject areas

Ecology, Evolution, Behavior and Systematics
Genetics
Cell Biology

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10.1186/s13059-025-03812-2

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title = "Loss of IDH1 and IDH2 mutations during the evolution of metastatic chondrosarcoma",

abstract = "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.",

keywords = "Bone tumor, Cancer evolution, Chondrosarcoma, IDH1, IDH2, Metastasis",

author = "\{PEACE Consortium\} and William Cross and Iben Lyskj{\ae}r and Christopher Davies and Abigail Bunkum and Rocha, \{Ana Maia\} and Tom Lesluyes and Fernanda Amary and Roberto Tirabosco and Cristina Naceur-Lombardelli and Rachel Leslie and Hayley Bridger and Laura Farrelly and Kitty Chan and Abby Sharp and Allan Hackshaw and Mairead McKenzie and Blanche Hampton and Iain McNeish and Tania Fernandes and Samantha Holden and Sanjay Jogai and Ian Tomlinson and Rodelaine Wilson and Bernard Olisemeke and Peter Colloby and Salma Kadiri and Joanne Webb and Gary Middleton and Amy Kerr and Hollie Bancroft and Charlotte Ferris and Peter Cockcroft and Martin Collard and Andrew Robinson and Gerald Langman and Bruce Tanchel and Shobhit Baijal and Babu Naidu and Jacqui Shaw and Dean Fennell and Anne Thomas and Jo Dransfield and Mat Carter and Fabio Gomes and Caroline Dive and Ana Ortega-Franco and Pedro Oliveira and Yvonne Summers and Fiona Blackhall and \{Van Loo\}, Peter",

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doi = "10.1186/s13059-025-03812-2",

language = "English (US)",

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AU - Cross, William

AU - Lyskjær, Iben

AU - Davies, Christopher

AU - Bunkum, Abigail

AU - Rocha, Ana Maia

AU - Lesluyes, Tom

AU - Amary, Fernanda

AU - Tirabosco, Roberto

AU - Naceur-Lombardelli, Cristina

AU - Leslie, Rachel

AU - Bridger, Hayley

AU - Farrelly, Laura

AU - Chan, Kitty

AU - Sharp, Abby

AU - Hackshaw, Allan

AU - McKenzie, Mairead

AU - Hampton, Blanche

AU - McNeish, Iain

AU - Fernandes, Tania

AU - Holden, Samantha

AU - Jogai, Sanjay

AU - Tomlinson, Ian

AU - Wilson, Rodelaine

AU - Olisemeke, Bernard

AU - Colloby, Peter

AU - Kadiri, Salma

AU - Webb, Joanne

AU - Middleton, Gary

AU - Kerr, Amy

AU - Bancroft, Hollie

AU - Ferris, Charlotte

AU - Cockcroft, Peter

AU - Collard, Martin

AU - Robinson, Andrew

AU - Langman, Gerald

AU - Tanchel, Bruce

AU - Baijal, Shobhit

AU - Naidu, Babu

AU - Shaw, Jacqui

AU - Fennell, Dean

AU - Thomas, Anne

AU - Dransfield, Jo

AU - Carter, Mat

AU - Gomes, Fabio

AU - Dive, Caroline

AU - Ortega-Franco, Ana

AU - Oliveira, Pedro

AU - Summers, Yvonne

AU - Blackhall, Fiona

AU - Van Loo, Peter

PY - 2025/12

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AB - 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.

KW - Bone tumor

KW - Cancer evolution

KW - Chondrosarcoma

KW - IDH1

KW - IDH2

KW - Metastasis

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SN - 1474-7596

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JO - Genome biology

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Loss of IDH1 and IDH2 mutations during the evolution of metastatic chondrosarcoma

Abstract

Keywords

ASJC Scopus subject areas

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