PTEN公司
外显子组测序
转移性乳腺癌
富维斯特朗
外显子组
生物
乳腺癌
转录组
癌症研究
基因表达谱
蛋白质组学
癌症
拷贝数变化
蛋白质组
转移
蛋白质基因组学
计算生物学
小桶
基因
肿瘤科
生物信息学
遗传学
突变
雌激素受体
基因组
基因表达
PI3K/AKT/mTOR通路
细胞凋亡
作者
Argun Akcakanat,Xiaofeng Zheng,Christian X. Cruz Pico,Tae-Beom Kim,Ken Chen,Anil Korkut,Aysegul A. Sahin,Vijaykumar Holla,Emily Tarco,Gopal Singh,Senthilkumar Damodaran,Gordon B. Mills,Ana M. Gonzalez-Angulo,Funda Meric-Bernstam
标识
DOI:10.1158/1078-0432.ccr-20-4048
摘要
Metastatic breast cancer (MBC) is not curable and there is a growing interest in personalized therapy options. Here we report molecular profiling of MBC focusing on molecular evolution in actionable alterations.Sixty-two patients with MBC were included. An analysis of DNA, RNA, and functional proteomics was done, and matched primary and metastatic tumors were compared when feasible.Targeted exome sequencing of 41 tumors identified common alterations in TP53 (21; 51%) and PIK3CA (20; 49%), as well as alterations in several emerging biomarkers such as NF1 mutations/deletions (6; 15%), PTEN mutations (4; 10%), and ARID1A mutations/deletions (6; 15%). Among 27 hormone receptor-positive patients, we identified MDM2 amplifications (3; 11%), FGFR1 amplifications (5; 19%), ATM mutations (2; 7%), and ESR1 mutations (4; 15%). In 10 patients with matched primary and metastatic tumors that underwent targeted exome sequencing, discordances in actionable alterations were common, including NF1 loss in 3 patients, loss of PIK3CA mutation in 1 patient, and acquired ESR1 mutations in 3 patients. RNA sequencing in matched samples confirmed loss of NF1 expression with genomic NF1 loss. Among 33 patients with matched primary and metastatic samples that underwent RNA profiling, 14 actionable genes were differentially expressed, including antibody-drug conjugate targets LIV-1 and B7-H3.Molecular profiling in MBC reveals multiple common as well as less frequent but potentially actionable alterations. Genomic and transcriptional profiling demonstrates intertumoral heterogeneity and potential evolution of actionable targets with tumor progression. Further work is needed to optimize testing and integrated analysis for treatment selection.
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