A Signaling Pathway Mediating Downregulation of BCL6 in Germinal Center B Cells Is Blocked by BCL6 Gene Alterations in B Cell Lymphoma

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• 作者：Masumichi Saito ; Jie Gao ; Katia Basso ; Yukiko Kitagawa ; Paula M. Smith ; Govind Bhagat ; Aless ; ra Pernis ; Laura Pasqualucci ; Riccardo Dalla-Favera
• 关键词：CELLCYCLE
• 刊名：Cancer Cell
• 出版年：2007
• 出版时间：16 October 2007
• 年：2007
• 卷：12
• 期：4
• 页码：403
• 全文大小：34 K

文摘

A large-scale RNA interference screen to discover genes involved in trastuzumab resistance in breast cancer identified only PTEN as a modulator of drug sensitivity. Oncogenic mutants of PIK3CA (activator of the same pathway and frequently mutated in breast cancer) also conferred resistance to trastuzumab in cell culture. In a cohort of 55 breast cancer patients, activation of the PI3K pathway, as judged by the presence of oncogenic PIK3CA mutations or low PTEN expression, was associated with poor prognosis after trastuzumab therapy, and the combined analysis of PTEN and PIK3CA identified twice as many patients at increased risk for progression compared to PTEN alone. Thus, assessment of PI3K pathway activation may provide a biomarker to identify patients unlikely to respond to trastuzumab-based therapy.