Erdheim-Chester disease associated with a novel, complex BRAF p.Thr599_Val600delinsArgGlu mutation
BRAF mutation testing to determine eligibility for treatment with vemurafenib was performed on archival skin lesions of a 54-year-old patient diagnosed with Erdheim-Chester disease (ECD) in 1999. Sanger sequencing of DNA extracted from a 2008 skin lesion identified two non-contiguous base substituti...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
| Published: |
British Medical Journal Publishing Group
2017
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| Online Access: | http://hdl.handle.net/20.500.11937/53296 |
| _version_ | 1848759110090096640 |
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| author | Bentel, J. Thomas, M. Rodgers, J. Arooj, Mahreen Gray, E. Allcock, R. Fermoyle, S. Mancera, R. Cannell, P. Parry, J. |
| author_facet | Bentel, J. Thomas, M. Rodgers, J. Arooj, Mahreen Gray, E. Allcock, R. Fermoyle, S. Mancera, R. Cannell, P. Parry, J. |
| author_sort | Bentel, J. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | BRAF mutation testing to determine eligibility for treatment with vemurafenib was performed on archival skin lesions of a 54-year-old patient diagnosed with Erdheim-Chester disease (ECD) in 1999. Sanger sequencing of DNA extracted from a 2008 skin lesion identified two non-contiguous base substitutions in BRAF, which were shown by next-generation sequencing (NGS) to be located in the same allele. Due to its long-standing duration, molecular evolution of disease was possible; however, both Sanger and NGS of a 2000 skin lesion were unsuccessful due to the poor quality of DNA. Finally, droplet digital PCR using a probe specific for this novel mutation detected the complex BRAF mutation in both the 2000 and 2008 lesions, indicating this case to be ECD with a novel underlying BRAF p.Thr599-Val600delinsArgGlu mutation. Although well at present, molecular modelling of the mutant BRAF suggests suboptimal binding of vemurafenib and hence reduced therapeutic effectiveness. |
| first_indexed | 2025-11-14T09:54:40Z |
| format | Journal Article |
| id | curtin-20.500.11937-53296 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:54:40Z |
| publishDate | 2017 |
| publisher | British Medical Journal Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-532962017-10-24T05:48:48Z Erdheim-Chester disease associated with a novel, complex BRAF p.Thr599_Val600delinsArgGlu mutation Bentel, J. Thomas, M. Rodgers, J. Arooj, Mahreen Gray, E. Allcock, R. Fermoyle, S. Mancera, R. Cannell, P. Parry, J. BRAF mutation testing to determine eligibility for treatment with vemurafenib was performed on archival skin lesions of a 54-year-old patient diagnosed with Erdheim-Chester disease (ECD) in 1999. Sanger sequencing of DNA extracted from a 2008 skin lesion identified two non-contiguous base substitutions in BRAF, which were shown by next-generation sequencing (NGS) to be located in the same allele. Due to its long-standing duration, molecular evolution of disease was possible; however, both Sanger and NGS of a 2000 skin lesion were unsuccessful due to the poor quality of DNA. Finally, droplet digital PCR using a probe specific for this novel mutation detected the complex BRAF mutation in both the 2000 and 2008 lesions, indicating this case to be ECD with a novel underlying BRAF p.Thr599-Val600delinsArgGlu mutation. Although well at present, molecular modelling of the mutant BRAF suggests suboptimal binding of vemurafenib and hence reduced therapeutic effectiveness. 2017 Journal Article http://hdl.handle.net/20.500.11937/53296 10.1136/bcr-2017-219720 British Medical Journal Publishing Group restricted |
| spellingShingle | Bentel, J. Thomas, M. Rodgers, J. Arooj, Mahreen Gray, E. Allcock, R. Fermoyle, S. Mancera, R. Cannell, P. Parry, J. Erdheim-Chester disease associated with a novel, complex BRAF p.Thr599_Val600delinsArgGlu mutation |
| title | Erdheim-Chester disease associated with a novel, complex BRAF p.Thr599_Val600delinsArgGlu mutation |
| title_full | Erdheim-Chester disease associated with a novel, complex BRAF p.Thr599_Val600delinsArgGlu mutation |
| title_fullStr | Erdheim-Chester disease associated with a novel, complex BRAF p.Thr599_Val600delinsArgGlu mutation |
| title_full_unstemmed | Erdheim-Chester disease associated with a novel, complex BRAF p.Thr599_Val600delinsArgGlu mutation |
| title_short | Erdheim-Chester disease associated with a novel, complex BRAF p.Thr599_Val600delinsArgGlu mutation |
| title_sort | erdheim-chester disease associated with a novel, complex braf p.thr599_val600delinsargglu mutation |
| url | http://hdl.handle.net/20.500.11937/53296 |