美国国家卫生研究院研究人员日前利用DNA测序技术确认了一组与黑色素瘤相关的基因变异。研究人员称，其中部分变异基因正是目前一种乳腺癌治疗药物的靶点。
研究人员首先对29名转移性黑色素瘤患者的肿瘤样本和血样中负责编码蛋白酪氨酸激酶的系列基因进行了测序，并确认其中有19个基因发生了变异。
研究人员随后扩大了研究范围，对79名转移性黑色素瘤患者的上述19个“嫌疑”基因进行了详细分析。他们发现，其中一种名为ERBB4的基因出现变异的情况最多，几乎五分之一的患者体内ERBB4基因都发生了变异。
在进一步的实验室研究中，他们发现黑色素瘤细胞的生长依赖于ERBB4基因变异的存在，而ERBB4基因抑制药物拉帕替尼可减缓黑色素瘤细胞的生长。拉帕替尼是一种治疗乳腺癌的药物。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Genetics 30 August 2009 | doi:10.1038/ng.438
Analysis of the tyrosine kinome in melanoma reveals recurrent mutations in ERBB4
Todd D Prickett1, Neena S Agrawal1, Xiaomu Wei1, Kristin E Yates1, Jimmy C Lin2, John R Wunderlich3, Julia C Cronin1, Pedro Cruz4, NISC Comparative Sequencing Program5, Steven A Rosenberg3 & Yardena Samuels1
Tyrosine phosphorylation is important in signaling pathways underlying tumorigenesis. We performed a mutational analysis of the protein tyrosine kinase (PTK) gene family in cutaneous metastatic melanoma. We identified 30 somatic mutations affecting the kinase domains of 19 PTKs and subsequently evaluated the entire coding regions of the genes encoding these 19 PTKs for somatic mutations in 79 melanoma samples. We found ERBB4 mutations in 19% of individuals with melanoma and found mutations in two other kinases (FLT1 and PTK2B) in 10% of individuals with melanomas. We examined seven missense mutations in the most commonly altered PTK gene, ERBB4, and found that they resulted in increased kinase activity and transformation ability. Melanoma cells expressing mutant ERBB4 had reduced cell growth after shRNA-mediated knockdown of ERBB4 or treatment with the ERBB inhibitor lapatinib. These studies could lead to personalized therapeutics specifically targeting the kinases that are mutationally altered in individual melanomas.
1 Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA.
2 The Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland, USA.
3 Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland, USA.
4 Genome Technology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
5 NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
