Somatic Mutation Profile by Next Generation Sequencing in HER2+ Breast Cancer

The HER pathway is the driving force behind 30% of human breast cancers. It is important to understand how targeted therapies block different cellular pathways, and mechanisms of escape from this blockage. Therapies directed at HER2 establish a successful treatment paradigm, but de novo and acquired resistance exist. The HER signaling system is a complex network with four receptors and eleven ligands, a phosphorylation signaling cascade, and many transcription factors, all complicated by both positive and negative feedback circuits. Analysis of genomes, exomes and transcriptomes by next generation sequencing is aimed at uncovering the genetic factors responsible for patient responses to HER2-directed therapies. We are sequencing HER2-overexpressing cancers, in order to identify potential somatic changes that may better select patients who will benefit from therapy, to determine new targets that may overcome resistance, and to improve outcomes with known... (for more see dbGaP study page.)

HER通路（HER pathway）是约30%人类乳腺癌的核心驱动因素。明确靶向疗法如何阻断不同细胞通路，以及肿瘤规避此类阻断的机制，具有重要研究价值。针对人表皮生长因子受体2（HER2）的疗法已构建起成熟的治疗范式，但原发性耐药（de novo resistance）与获得性耐药（acquired resistance）依然存在。HER信号系统是一套复杂的调控网络，包含4种受体、11种配体、一套磷酸化信号级联反应以及众多转录因子，同时还兼具正负反馈环路，进一步加剧了系统的复杂度。通过下一代测序（next generation sequencing）对基因组、外显子组与转录组进行分析，旨在揭示影响患者对HER2靶向疗法应答的遗传因素。本研究正针对HER2过表达癌症开展测序工作，以期识别潜在的体细胞变异，从而更精准地筛选出可从该疗法中获益的患者；同时确定可克服耐药性的全新治疗靶点，并优化现有疗法的治疗效果……（更多详情请参见dbGaP研究页面）