Genomic discovery of skin cancer subtypes provides potential ‘signpost’ for drug targets
MD Anderson News Release June 18, 2015
MD Anderson researchers lead The Cancer Genome Atlas analysis of cutaneous melanoma identifying four subtypes
MD Anderson News Release 06/18/2015
Cutaneous melanoma, the most deadly form of skin cancer, is now believed to be divided into four distinct genomic subtypes, say researchers atThe University of Texas MD Anderson Cancer Center, a finding that could prove valuable in the ever-increasing pursuit of personalized medicine.
作为...的一部分癌症基因组图谱中，188bet体育网址研究人员确定了四个黑素瘤亚型：BRAF，RAS，NF1和Triple-WT，这是由从331名患者获得的样品的分析存在或不存在的突变的限定。在五年的研究结果从五个以上的国家，包括澳大利亚，德国和加拿大超过300名研究人员组成的国际合作。188bet体育网址
“在临床管理病人晚期黑色素瘤的主要成就是有效的靶向治疗的发展，”杰弗里E. Gershenwald，医学博士，外科教授，肿瘤外科说。“这一综合性黑色素瘤的分类使我们能够创建可用于框架进一步个性化的治疗决策中都针对性和免疫治疗领域，以及开发更多有影响力的预后和预测模型，以告知病人护理。”
从研究结果发表在2015年6月18日发行细胞。Analysis of the TCGA effort was chaired by Gershenwald, Ian Watson, Ph.D., instructor of Genomic Medicine and Lynda Chin, M.D., former chair of Genomic Medicine and now associate vice chancellor for health transformation and chief innovation officer for health affairs at The UT System. Gershenwald is also co-leader of MD Anderson’s黑色素瘤登月计划，其目的是加速科学发现转化为临床应用进展和显著减少癌症死亡。
The scientists found all four genomic subtypes share common “downstream” signaling pathways, but differ in how they activate these pathways. Understanding the genomic underpinnings of melanoma may provide additional information on other existing therapies.
“For example, BRAF and MEK inhibitor combinations are now used to treat patients with BRAF mutant melanomas, and MEK inhibitor combinations are being explored for RAS mutant melanomas,” said Watson. “Pre-clinical studies have already demonstrated that some NF1 melanoma cell lines respond to MEK inhibitors, but more work is needed to identify responders and non-responders within this new melanoma subtype, as well as to determine strategies to treat Triple Wild-type melanoma patients.”
有趣的是，没有显著相关性的基因组亚型和患者结果之间找到。然而，每个基因组亚型中，研究人员发现，与改善生存相关成分没有免疫浸润的证据的188bet体育网址一个子集。
“Detailed analyses showed that these lymphocytic elements were not merely ‘bystanders,’” said Chin. “They had infiltrated the tumor and were likely associated with melanoma biology.” The study also revealed the importance of a T cell biomarker called LCK, a protein found in lymphocytes or white blood cells. The biomarker was shown to be associated with improved patient survival.
The team hypothesizes that this information could prove useful in the emerging field of immunotherapy, which has shown success in treating late-stage melanoma patients. In particular, recently approved checkpoint blockade drugs have shown incredible potential in treatment for melanomas. Yet, it is not entirely clear which patients respond to the therapy.
“我们相信来自世界各地，其中包括谁分析免疫浸润样品病理学家20多个组织来源站点和50个机构这种国际合作，谁确定显著驾驶遗传改变计算生物学家和临床科学家们谁在获取样本和解释数据辅助，已经产生的数据集是一个宝库，这将种子多年的研究来，”齐秦说。“我们不能没有谁通过参与研究的协议捐赠样本家属和患者进行了这项研究。”188bet体育网址
这项研究是由美国国立卫生研究院（U54HG003273，U54HG003067，U54HG003079，U24CA143799，U24CA143835，U24CA143840，U24CA143843，U24CA143845，U24CA143848，U24CA143858，U24CA143866，U24CA143867，U24CA143882，U24CA143883，U24CA144025和P30CA016672资助。