Department of Molecular, Cell and Cancer Biology.
Department of Surgery.
JCI Insight. 2018 Apr 19;3(8). doi: 10.1172/jci.insight.97398.
Pleomorphic invasive lobular carcinoma (PILC) is an aggressive variant of invasive lobular breast cancer that is associated with poor clinical outcomes. Limited molecular data are available to explain the mechanistic basis for PILC behavior. To address this issue, targeted sequencing was performed to identify molecular alterations that define PILC. This sequencing analysis identified genes that distinguish PILC from classic ILC and invasive ductal carcinoma by the incidence of their genomic changes. In particular, insulin receptor substrate 2 (IRS2) is recurrently mutated in PILC, and pathway analysis reveals a role for the insulin receptor (IR)/insulin-like growth factor-1 receptor (IGF1R)/IRS2 signaling pathway in PILC. IRS2 mutations identified in PILC enhance invasion, revealing a role for this signaling adaptor in the aggressive nature of PILC.
多形性浸润性小叶癌（PILC）是一种侵袭性小叶乳腺癌的变体，与不良的临床结局相关。目前可用的分子数据有限，无法解释 PILC 行为的机制基础。为了解决这个问题，进行了靶向测序，以确定定义 PILC 的分子改变。这项测序分析确定了通过基因组变化发生率将 PILC 与经典 ILC 和浸润性导管癌区分开来的基因。特别是胰岛素受体底物 2（IRS2）在 PILC 中经常发生突变，通路分析显示胰岛素受体（IR）/胰岛素样生长因子-1 受体（IGF1R）/IRS2 信号通路在 PILC 中起作用。在 PILC 中鉴定的 IRS2 突变增强了侵袭性，揭示了这种信号接头在 PILC 侵袭性中的作用。
