Vivancos Ana, Caratú Ginevra, Matito Judit, Muñoz Eva, Ferrer Berta, Hernández-Losa Javier, Bodet Domingo, Pérez-Alea Mileidys, Cortés Javier, Garcia-Patos Vicente, Recio Juan A
Cancer Genomics Group Translational Research Program, Vall dHebron Institute of Oncology-VHIO, Vall dHebron Hospital, Barcelona, Spain.
Clinical Oncology Program, Vall dHebron Hospital, Barcelona, Spain.
Pigment Cell Melanoma Res. 2016 Mar;29(2):247-53. doi: 10.1111/pcmr.12452.
Melanoma presents molecular alterations based on its anatomical location and exposure to environmental factors. Due to its intrinsic genetic heterogeneity, a simple snapshot of a tumor's genetic alterations does not reflect the tumor clonal complexity or specific gene-gene cooperation. Here, we studied the genetic alterations and clonal evolution of a unique patient with a Nevus of Ota that developed into a recurring uveal-like dermal melanoma. The Nevus of Ota and ulterior lesions contained GNAQ mutations were c-KIT positive, and tumors showed an increased RAS pathway activity during progression. Whole-exome sequencing of these lesions revealed the acquisition of BAP1 and TP53 mutations during tumor evolution, thereby unmasking clonal heterogeneity and allowing the identification of cooperating genes within the same tumor. Our results highlight the importance of studying tumor genetic evolution to identify cooperating mechanisms and delineate effective therapies.
黑色素瘤根据其解剖位置和暴露于环境因素的情况呈现出分子改变。由于其内在的基因异质性，肿瘤基因改变的简单快照并不能反映肿瘤的克隆复杂性或特定的基因-基因协同作用。在此，我们研究了一名独特患者的基因改变和克隆进化，该患者的太田痣发展为复发性葡萄膜样皮肤黑色素瘤。太田痣及后续病变含有GNAQ突变，c-KIT呈阳性，并且肿瘤在进展过程中显示出RAS通路活性增加。对这些病变进行全外显子测序揭示了肿瘤进化过程中BAP1和TP53突变的获得，从而揭示了克隆异质性，并允许在同一肿瘤内鉴定协同基因。我们的结果强调了研究肿瘤基因进化以确定协同机制和描绘有效治疗方法的重要性。
