Intratumoral molecular heterogeneity in a BRAF-mutant, BRAF inhibitor-resistant melanoma

A case illustrating the challenges for personalized medicine

James S. Wilmott, Varsha Tembe, Julie R. Howle, Raghwa Sharma, John F. Thompson, Helen Rizos, Roger S. Lo, Richard F. Kefford, Richard A. Scolyer, Georgina V. Long*

*Corresponding author for this work

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Targeted therapies are increasingly being used to treat a variety of cancers. Their efficacy depends upon the accurate detection and targeting of a specific mutation or aberration in the tumor. All cancers, such as melanoma, are molecularly heterogeneous, with drug-resistant subclones present before the treatment or emerging as a result of targeted therapies. Here, we show intralesional molecular heterogeneity in a progressing V600E BRAF-mutant melanoma metastasis from a patient treated for 7 months with the BRAF inhibitor vemurafenib. In the single metastasis, two distinct subclones were observed, both V600E BRAFmutant and only one with an additional G13R NRAS mutation. Molecular heterogeneity even at the intralesional level shows that personalizing or adjusting therapies based on genotyping of a portion of a single lesion may not accurately depict the molecular profile or drivers of oncogenesis across the entire patient's melanoma.

Original languageEnglish
Pages (from-to)2704-2708
Number of pages5
JournalMolecular Cancer Therapeutics
Volume11
Issue number12
DOIs
Publication statusPublished - Dec 2012
Externally publishedYes

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