美國(guó)國(guó)家衛(wèi)生研究院研究人員日前利用DNA測(cè)序技術(shù)確認(rèn)了一組與黑色素瘤相關(guān)的基因變異,。研究人員稱，其中部分變異基因正是目前一種乳腺癌治療藥物的靶點(diǎn),。
研究人員首先對(duì)29名轉(zhuǎn)移性黑色素瘤患者的腫瘤樣本和血樣中負(fù)責(zé)編碼蛋白酪氨酸激酶的系列基因進(jìn)行了測(cè)序,，并確認(rèn)其中有19個(gè)基因發(fā)生了變異。
研究人員隨后擴(kuò)大了研究范圍,，對(duì)79名轉(zhuǎn)移性黑色素瘤患者的上述19個(gè)“嫌疑”基因進(jìn)行了詳細(xì)分析,。他們發(fā)現(xiàn),，其中一種名為ERBB4的基因出現(xiàn)變異的情況最多，幾乎五分之一的患者體內(nèi)ERBB4基因都發(fā)生了變異,。
在進(jìn)一步的實(shí)驗(yàn)室研究中,，他們發(fā)現(xiàn)黑色素瘤細(xì)胞的生長(zhǎng)依賴于ERBB4基因變異的存在，而ERBB4基因抑制藥物拉帕替尼可減緩黑色素瘤細(xì)胞的生長(zhǎng),。拉帕替尼是一種治療乳腺癌的藥物,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
