Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, 44-101, Poland.
Chemotherapy Day Unit, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, 44-101, Poland.
J Cancer Res Clin Oncol. 2024 Sep 28;150(9):433. doi: 10.1007/s00432-024-05957-2.
In the era of next-generation sequencing, the genetic background of cancer, including melanoma, appears to be thoroughly established. However, evaluating the oncogene BRAF mutation in codon V600 is still the only companion diagnostic genomic test commonly implemented in clinics for molecularly targeted treatment of advanced melanoma. Are we wasting the collected genomic data? Will we implement our current genomic knowledge of melanoma in clinics soon? This question is rather urgent because new therapeutic targets and biomarkers are needed to implement more personalized, patient-tailored therapy in clinics. Here, we provide an update on the molecular background of melanoma, including a description of four already established molecular subtypes: BRAF+, NRAS+, NF1+, and triple WT, as well as relatively new NGS-derived melanoma genes such as PREX2, ERBB4, PPP6C, FBXW7, PIK3CA, and IDH1. We also present a comparison of genomic profiles obtained in recent years with a focus on the most common melanoma genes. Finally, we propose our melanoma gene panel consisting of 22 genes that, in our opinion, are "must-have" genes in both melanoma-specific genomic tests and pan-cancer tests established to improve the treatment of melanoma further.
在下一代测序时代,癌症(包括黑色素瘤)的遗传背景似乎已经得到了充分的阐明。然而,评估 BRAF 基因 V600 密码子突变仍然是临床中用于晚期黑色素瘤分子靶向治疗的唯一常用伴随诊断基因组检测。我们是否在浪费收集到的基因组数据?我们是否很快就能将目前对黑色素瘤的基因组认识应用于临床?这个问题相当紧迫,因为需要新的治疗靶点和生物标志物,以便在临床中实施更具个性化、更符合患者需求的治疗。在这里,我们提供了黑色素瘤分子背景的最新信息,包括已经确立的四个分子亚型(BRAF+、NRAS+、NF1+和三重 WT)的描述,以及相对较新的基于 NGS 的黑色素瘤基因,如 PREX2、ERBB4、PPP6C、FBXW7、PIK3CA 和 IDH1。我们还比较了近年来获得的基因组图谱,重点关注最常见的黑色素瘤基因。最后,我们提出了我们的黑色素瘤基因panel,包含 22 个基因,我们认为这些基因是黑色素瘤特异性基因组检测和泛癌检测中“必备”的基因,旨在进一步改善黑色素瘤的治疗效果。