Erdheim-Chester disease associated with a novel, complex BRAF p.Thr599-Val600delinsArgGlu mutation

Document Type

Journal Article

Publication Title

BMJ Case Reports

Publisher

BMJ Group

Place of Publication

United Kingdom

School

School of Medical and Health Sciences

RAS ID

27350

Comments

Bentel, J. M., Thomas, M. A., Rodgers, J. J., Arooj, M., Gray, E., Allcock, R., ... Parry, J. (2017). Erdheim–Chester disease associated with a novel, complex BRAF p. Thr599_Val600delinsArgGlu mutation. BMJ Case Reports, 2017, bcr-2017. http://dx.doi.org/10.1136/bcr-2017-219720

Abstract

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.

DOI

10.1136/bcr-2017-219720

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