主讲人：吴华君 北京大学研究员
时间：2021年3月19日14：00
地点：三号楼332会议厅
举办单位：数理学院
内容介绍：Intra-tumor heterogeneity (ITH) of human tumors is increasingly recognized as being important for tumor progression, treatment response, and drug resistance. However, the spatial distribution of ITH remains incompletely understood, as prior technologies have not allowed for simultaneous measurements of molecular and spatial features of tumor samples in a high-throughput manner. Here, we present spatial analysis of ITH in lung adenocarcinomas from 147 patients by using multi-region mass spectrometry, single cell copy number sequencing and cyclic immunofluorescence. By profiling thousands of regions/single cells we identified two distinct spatial patterns, termed clustered and random geographic diversification (GD). These patterns were observed in similar positions using both proteomic and genomic data. The random proteomic GD pattern, which is characterized by decreased cell adhesion and increased immune activity, was significantly associated with increased risk of recurrence or death in two independent patient cohorts. We also elucidated the effects of the tumor-immune environment and key genetic alterations on different GD patterns. This study presents comprehensive spatial mapping of ITH in lung adenocarcinoma and provides unexpected insight into the clinical consequences of geographic diversification of intratumor heterogeneity.