PT - JOURNAL ARTICLE AU - Wilmott, James S. AU - Tembe, Varsha AU - Howle, Julie R. AU - Sharma, Raghwa AU - Thompson, John F. AU - Rizos, Helen AU - Lo, Roger S. AU - Kefford, Richard F. AU - Scolyer, Richard A. AU - Long, Georgina V. TI - Intratumoral Molecular Heterogeneity in a <em>BRAF</em>-Mutant, BRAF Inhibitor-Resistant Melanoma: A Case Illustrating the Challenges for Personalized Medicine AID - 10.1158/1535-7163.MCT-12-0530 DP - 2012 Dec 01 TA - Molecular Cancer Therapeutics PG - 2704--2708 VI - 11 IP - 12 4099 - http://mct.aacrjournals.org/content/11/12/2704.short 4100 - http://mct.aacrjournals.org/content/11/12/2704.full SO - Mol Cancer Ther2012 Dec 01; 11 AB - 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 BRAF-mutant 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. Mol Cancer Ther; 11(12); 2704–8. ©2012 AACR.