GRCh38 · COSMIC v97


This section shows a summary for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.

The mutational landscape of melanoma brain metastases presenting as the first visceral site of recurrence.
Paper ID
Rabbie R, Ferguson P, Wong K, Couturier DL, Moran U, Turner C, Emanuel P, Haas K, Saunus JM, Davidson MR, Lakhani SR, Shivalingam B, Long GV, Parkinson C, Osman I, Scolyer RA, Corrie P and Adams DJ
Experimental Cancer Genetics, The Wellcome Sanger Institute, Hinxton, Cambridgeshire, UK.
British journal of cancer, 2020
ISSN: 1532-1827
PMID: 33024263 (view at PubMed or Europe PMC)
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 BRAF<sup>V600</sup>, 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.
Paper Status