<i>IDH</i> Mutations in Chondrosarcoma: Case Closed or Not?
Chondrosarcomas are malignant cartilage-producing tumours that frequently harbour isocitrate dehydrogenase 1 and -2 (<i>IDH</i>) gene mutations. Several studies have confirmed that these mutations are key players in the early stages of cartilage tumour development, but their role in late...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/14/3603 |
| _version_ | 1797589990114328576 |
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| author | Sanne Venneker Judith V. M. G. Bovée |
| author_facet | Sanne Venneker Judith V. M. G. Bovée |
| author_sort | Sanne Venneker |
| collection | DOAJ |
| description | Chondrosarcomas are malignant cartilage-producing tumours that frequently harbour isocitrate dehydrogenase 1 and -2 (<i>IDH</i>) gene mutations. Several studies have confirmed that these mutations are key players in the early stages of cartilage tumour development, but their role in later stages remains ambiguous. The prognostic value of <i>IDH</i> mutations remains unclear and preclinical studies have not identified effective treatment modalities (in)directly targeting these mutations. In contrast, the <i>IDH</i> mutation status is a prognostic factor in other cancers, and IDH mutant inhibitors as well as therapeutic strategies targeting the underlying vulnerabilities induced by <i>IDH</i> mutations seem effective in these tumour types. This discrepancy in findings might be ascribed to a difference in tumour type, elevated D-2-hydroxyglutarate levels, and the type of in vitro model (endogenous vs. genetically modified) used in preclinical studies. Moreover, recent studies suggest that the (epi)genetic landscape in which the <i>IDH</i> mutation functions is an important factor to consider when investigating potential therapeutic strategies or patient outcomes. These findings imply that the dichotomy between <i>IDH</i> wildtype and mutant is too simplistic and additional subgroups indeed exist within chondrosarcoma. Future studies should focus on the identification, characterisation, and tailoring of treatments towards these biological subgroups within <i>IDH</i> wildtype and mutant chondrosarcoma. |
| first_indexed | 2024-03-11T01:13:59Z |
| format | Article |
| id | doaj.art-cf755eac970b4890a13b7d4dbe8d3efb |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T01:13:59Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-cf755eac970b4890a13b7d4dbe8d3efb2023-11-18T18:41:27ZengMDPI AGCancers2072-66942023-07-011514360310.3390/cancers15143603<i>IDH</i> Mutations in Chondrosarcoma: Case Closed or Not?Sanne Venneker0Judith V. M. G. Bovée1Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsChondrosarcomas are malignant cartilage-producing tumours that frequently harbour isocitrate dehydrogenase 1 and -2 (<i>IDH</i>) gene mutations. Several studies have confirmed that these mutations are key players in the early stages of cartilage tumour development, but their role in later stages remains ambiguous. The prognostic value of <i>IDH</i> mutations remains unclear and preclinical studies have not identified effective treatment modalities (in)directly targeting these mutations. In contrast, the <i>IDH</i> mutation status is a prognostic factor in other cancers, and IDH mutant inhibitors as well as therapeutic strategies targeting the underlying vulnerabilities induced by <i>IDH</i> mutations seem effective in these tumour types. This discrepancy in findings might be ascribed to a difference in tumour type, elevated D-2-hydroxyglutarate levels, and the type of in vitro model (endogenous vs. genetically modified) used in preclinical studies. Moreover, recent studies suggest that the (epi)genetic landscape in which the <i>IDH</i> mutation functions is an important factor to consider when investigating potential therapeutic strategies or patient outcomes. These findings imply that the dichotomy between <i>IDH</i> wildtype and mutant is too simplistic and additional subgroups indeed exist within chondrosarcoma. Future studies should focus on the identification, characterisation, and tailoring of treatments towards these biological subgroups within <i>IDH</i> wildtype and mutant chondrosarcoma.https://www.mdpi.com/2072-6694/15/14/3603sarcomachondrosarcomaisocitrate dehydrogenase mutation<i>IDH1</i><i>IDH2</i>D-2-hydroxyglutarate |
| spellingShingle | Sanne Venneker Judith V. M. G. Bovée <i>IDH</i> Mutations in Chondrosarcoma: Case Closed or Not? Cancers sarcoma chondrosarcoma isocitrate dehydrogenase mutation <i>IDH1</i> <i>IDH2</i> D-2-hydroxyglutarate |
| title | <i>IDH</i> Mutations in Chondrosarcoma: Case Closed or Not? |
| title_full | <i>IDH</i> Mutations in Chondrosarcoma: Case Closed or Not? |
| title_fullStr | <i>IDH</i> Mutations in Chondrosarcoma: Case Closed or Not? |
| title_full_unstemmed | <i>IDH</i> Mutations in Chondrosarcoma: Case Closed or Not? |
| title_short | <i>IDH</i> Mutations in Chondrosarcoma: Case Closed or Not? |
| title_sort | i idh i mutations in chondrosarcoma case closed or not |
| topic | sarcoma chondrosarcoma isocitrate dehydrogenase mutation <i>IDH1</i> <i>IDH2</i> D-2-hydroxyglutarate |
| url | https://www.mdpi.com/2072-6694/15/14/3603 |
| work_keys_str_mv | AT sannevenneker iidhimutationsinchondrosarcomacaseclosedornot AT judithvmgbovee iidhimutationsinchondrosarcomacaseclosedornot |