Circulating tumour DNA is a promising biomarker for risk stratification of central chondrosarcoma with IDH1/2 and GNAS mutations

Chondrosarcoma (CS) is a rare tumour type and the most common primary malignant bone cancer in adults. The prognosis, currently based on tumour grade, imaging and anatomical location, is not reliable, and more objective biomarkers are required. We aimed to determine whether the level of circulating...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Iben Lyskjær, Christopher Davies, Anna‐Christina Strobl, Joanna Hindley, Steven James, Radhesh K. Lalam, William Cross, Geoff Hide, Kenneth S. Rankin, Lee Jeys, Roberto Tirabosco, Jonathan Stevenson, Genomics England Research Consortium, Paul O’Donnell, Paul Cool, Adrienne M. Flanagan
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	chondrosarcoma circulating tumour DNA GNAS IDH1 IDH2 prognosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/06050dfe09da4f93b0994c5d65b4ce29
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:06050dfe09da4f93b0994c5d65b4ce29
record_format	dspace
spelling	oai:doaj.org-article:06050dfe09da4f93b0994c5d65b4ce292021-12-02T10:31:06ZCirculating tumour DNA is a promising biomarker for risk stratification of central chondrosarcoma with IDH1/2 and GNAS mutations1878-02611574-789110.1002/1878-0261.13102https://doaj.org/article/06050dfe09da4f93b0994c5d65b4ce292021-12-01T00:00:00Zhttps://doi.org/10.1002/1878-0261.13102https://doaj.org/toc/1574-7891https://doaj.org/toc/1878-0261Chondrosarcoma (CS) is a rare tumour type and the most common primary malignant bone cancer in adults. The prognosis, currently based on tumour grade, imaging and anatomical location, is not reliable, and more objective biomarkers are required. We aimed to determine whether the level of circulating tumour DNA (ctDNA) in the blood of CS patients could be used to predict outcome. In this multi‐institutional study, we recruited 145 patients with cartilaginous tumours, of which 41 were excluded. ctDNA levels were assessed in 83 of the remaining 104 patients, whose tumours harboured a hotspot mutation in IDH1/2 or GNAS. ctDNA was detected pre‐operatively in 31/83 (37%) and in 12/31 (39%) patients postoperatively. We found that detection of ctDNA was more accurate than pathology for identification of high‐grade tumours and was associated with a poor prognosis; ctDNA was never associated with CS grade 1/atypical cartilaginous tumours (ACT) in the long bones, in neoplasms sited in the small bones of the hands and feet or in tumours measuring less than 80 mm. Although the results are promising, they are based on a small number of patients, and therefore, introduction of this blood test into clinical practice as a complementary assay to current standard‐of‐care protocols would allow the assay to be assessed more stringently and developed for a more personalised approach for the treatment of patients with CS.Iben LyskjærChristopher DaviesAnna‐Christina StroblJoanna HindleySteven JamesRadhesh K. LalamWilliam CrossGeoff HideKenneth S. RankinLee JeysRoberto TiraboscoJonathan StevensonGenomics England Research ConsortiumPaul O’DonnellPaul CoolAdrienne M. FlanaganWileyarticlechondrosarcomacirculating tumour DNAGNASIDH1IDH2prognosisNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Oncology, Vol 15, Iss 12, Pp 3679-3690 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	chondrosarcoma circulating tumour DNA GNAS IDH1 IDH2 prognosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	chondrosarcoma circulating tumour DNA GNAS IDH1 IDH2 prognosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Iben Lyskjær Christopher Davies Anna‐Christina Strobl Joanna Hindley Steven James Radhesh K. Lalam William Cross Geoff Hide Kenneth S. Rankin Lee Jeys Roberto Tirabosco Jonathan Stevenson Genomics England Research Consortium Paul O’Donnell Paul Cool Adrienne M. Flanagan Circulating tumour DNA is a promising biomarker for risk stratification of central chondrosarcoma with IDH1/2 and GNAS mutations
description	Chondrosarcoma (CS) is a rare tumour type and the most common primary malignant bone cancer in adults. The prognosis, currently based on tumour grade, imaging and anatomical location, is not reliable, and more objective biomarkers are required. We aimed to determine whether the level of circulating tumour DNA (ctDNA) in the blood of CS patients could be used to predict outcome. In this multi‐institutional study, we recruited 145 patients with cartilaginous tumours, of which 41 were excluded. ctDNA levels were assessed in 83 of the remaining 104 patients, whose tumours harboured a hotspot mutation in IDH1/2 or GNAS. ctDNA was detected pre‐operatively in 31/83 (37%) and in 12/31 (39%) patients postoperatively. We found that detection of ctDNA was more accurate than pathology for identification of high‐grade tumours and was associated with a poor prognosis; ctDNA was never associated with CS grade 1/atypical cartilaginous tumours (ACT) in the long bones, in neoplasms sited in the small bones of the hands and feet or in tumours measuring less than 80 mm. Although the results are promising, they are based on a small number of patients, and therefore, introduction of this blood test into clinical practice as a complementary assay to current standard‐of‐care protocols would allow the assay to be assessed more stringently and developed for a more personalised approach for the treatment of patients with CS.
format	article
author	Iben Lyskjær Christopher Davies Anna‐Christina Strobl Joanna Hindley Steven James Radhesh K. Lalam William Cross Geoff Hide Kenneth S. Rankin Lee Jeys Roberto Tirabosco Jonathan Stevenson Genomics England Research Consortium Paul O’Donnell Paul Cool Adrienne M. Flanagan
author_facet	Iben Lyskjær Christopher Davies Anna‐Christina Strobl Joanna Hindley Steven James Radhesh K. Lalam William Cross Geoff Hide Kenneth S. Rankin Lee Jeys Roberto Tirabosco Jonathan Stevenson Genomics England Research Consortium Paul O’Donnell Paul Cool Adrienne M. Flanagan
author_sort	Iben Lyskjær
title	Circulating tumour DNA is a promising biomarker for risk stratification of central chondrosarcoma with IDH1/2 and GNAS mutations
title_short	Circulating tumour DNA is a promising biomarker for risk stratification of central chondrosarcoma with IDH1/2 and GNAS mutations
title_full	Circulating tumour DNA is a promising biomarker for risk stratification of central chondrosarcoma with IDH1/2 and GNAS mutations
title_fullStr	Circulating tumour DNA is a promising biomarker for risk stratification of central chondrosarcoma with IDH1/2 and GNAS mutations
title_full_unstemmed	Circulating tumour DNA is a promising biomarker for risk stratification of central chondrosarcoma with IDH1/2 and GNAS mutations
title_sort	circulating tumour dna is a promising biomarker for risk stratification of central chondrosarcoma with idh1/2 and gnas mutations
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/06050dfe09da4f93b0994c5d65b4ce29
work_keys_str_mv	AT ibenlyskjær circulatingtumourdnaisapromisingbiomarkerforriskstratificationofcentralchondrosarcomawithidh12andgnasmutations AT christopherdavies circulatingtumourdnaisapromisingbiomarkerforriskstratificationofcentralchondrosarcomawithidh12andgnasmutations AT annachristinastrobl circulatingtumourdnaisapromisingbiomarkerforriskstratificationofcentralchondrosarcomawithidh12andgnasmutations AT joannahindley circulatingtumourdnaisapromisingbiomarkerforriskstratificationofcentralchondrosarcomawithidh12andgnasmutations AT stevenjames circulatingtumourdnaisapromisingbiomarkerforriskstratificationofcentralchondrosarcomawithidh12andgnasmutations AT radheshklalam circulatingtumourdnaisapromisingbiomarkerforriskstratificationofcentralchondrosarcomawithidh12andgnasmutations AT williamcross circulatingtumourdnaisapromisingbiomarkerforriskstratificationofcentralchondrosarcomawithidh12andgnasmutations AT geoffhide circulatingtumourdnaisapromisingbiomarkerforriskstratificationofcentralchondrosarcomawithidh12andgnasmutations AT kennethsrankin circulatingtumourdnaisapromisingbiomarkerforriskstratificationofcentralchondrosarcomawithidh12andgnasmutations AT leejeys circulatingtumourdnaisapromisingbiomarkerforriskstratificationofcentralchondrosarcomawithidh12andgnasmutations AT robertotirabosco circulatingtumourdnaisapromisingbiomarkerforriskstratificationofcentralchondrosarcomawithidh12andgnasmutations AT jonathanstevenson circulatingtumourdnaisapromisingbiomarkerforriskstratificationofcentralchondrosarcomawithidh12andgnasmutations AT genomicsenglandresearchconsortium circulatingtumourdnaisapromisingbiomarkerforriskstratificationofcentralchondrosarcomawithidh12andgnasmutations AT paulodonnell circulatingtumourdnaisapromisingbiomarkerforriskstratificationofcentralchondrosarcomawithidh12andgnasmutations AT paulcool circulatingtumourdnaisapromisingbiomarkerforriskstratificationofcentralchondrosarcomawithidh12andgnasmutations AT adriennemflanagan circulatingtumourdnaisapromisingbiomarkerforriskstratificationofcentralchondrosarcomawithidh12andgnasmutations
_version_	1718397101272989696

Circulating tumour DNA is a promising biomarker for risk stratification of central chondrosarcoma with IDH1/2 and GNAS mutations

Ejemplares similares