دورية أكاديمية
The mutational landscape of melanoma brain metastases presenting as the first visceral site of recurrence.
| العنوان: | The mutational landscape of melanoma brain metastases presenting as the first visceral site of recurrence. |
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| المؤلفون: | Rabbie, Roy, Ferguson, Peter, Wong, Kim, Couturier, Dominique-Laurent, Moran, Una, Turner, Clinton, Emanuel, Patrick, Haas, Kerstin, Saunus, Jodi M, Davidson, Morgan R, Lakhani, Sunil R, Shivalingam, Brindha, Long, Georgina V, Parkinson, Christine, Osman, Iman, Scolyer, Richard A, Corrie, Pippa, Adams, David J |
| بيانات النشر: | Springer Science and Business Media LLC //dx.doi.org/10.1038/s41416-020-01090-2 Br J Cancer |
| سنة النشر: | 2021 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Brain Neoplasms, DNA Mutational Analysis, Humans, Melanoma, Mutation, Proto-Oncogene Proteins p21(ras), Recurrence, Skin Neoplasms, Cutaneous Malignant |
| الوصف: | Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440Test ; Brain metastases are a major cause of melanoma-related mortality and morbidity. We undertook whole-exome sequencing of 50 tumours from patients undergoing surgical resection of brain metastases presenting as the first site of visceral disease spread and validated our findings in an independent dataset of 18 patients. Brain metastases had a similar driver mutational landscape to cutaneous melanomas in TCGA. However, KRAS was the most significantly enriched driver gene, with 4/50 (8%) of brain metastases harbouring non-synonymous mutations. Hotspot KRAS mutations were mutually exclusive from BRAFV600, NRAS and HRAS mutations and were associated with a reduced overall survival from the resection of brain metastases (HR 10.01, p = 0.001). Mutations in KRAS were clonal and concordant with extracranial disease, suggesting that these mutations are likely present within the primary. Our analyses suggest that KRAS mutations could help identify patients with primary melanoma at higher risk of brain metastases who may benefit from more intensive, protracted surveillance. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text/xml; application/pdf; application/zip |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/329090Test |
| DOI: | 10.17863/CAM.76536 |
| الإتاحة: | https://doi.org/10.17863/CAM.76536Test https://www.repository.cam.ac.uk/handle/1810/329090Test |
| رقم الانضمام: | edsbas.D331ECA |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.76536 |
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