Intratumoral molecular heterogeneity in a BRAF-mutant, BRAF inhibitor-resistant melanoma: a case illustrating the challenges for personalized medicine
Menée sur un échantillon métastatique prélevé sur un patient atteint d'un mélanome présentant la mutation BRAF-V600E et ayant été traité pendant sept mois à l'aide de vemurafenib, cette étude met en évidence une hétérogénéité moléculaire dans cette métastase
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 tumour. All cancers such as melanoma are molecularly heterogeneous, with drug resistant subclones present prior to treatment or emerging as a result of targeted therapies. Here we show intra-lesional 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 intra-lesional level demonstrates that personalising or adjusting therapies based on genotyping of a portion of a single lesion, might not accurately depict the molecular profile or drivers of oncogenesis across the entire patient's melanoma.
http://mct.aacrjournals.org/content/early/2012/09/06/1535-7163.MCT-12-0530.abstract 2012