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.