作者: Giuseppe Pelosi , Alessio Pellegrinelli , Alessandra Fabbri , Elena Tamborini , Federica Perrone
DOI: 10.1007/S00428-016-1931-Z
关键词: Tumor progression 、 KRAS 、 Somatic evolution in cancer 、 PTEN 、 Cancer research 、 Gene mutation 、 Adenocarcinoma 、 Wild type 、 Biology 、 Pathology 、 Mutation
摘要: While pulmonary adenocarcinoma (ADC) is morphologically heterogeneous, little known about intra-tumor gene mutation heterogeneity (ITH). We therefore subjected 20 ADC nodules, 5 mutated for EGFR and KRAS, with an ALK translocation, wild type (WT) these alterations, to unsupervised next-generation sequencing of tumor regions from diverse architectural patterns. When 2 or more different mutations were found in a single tumor, this fulfilled the criteria ITH. In 84 studied architecture, 71 34 WT profiles found. ITH was observed 9/15 (60 %) ADC, 3 EGFR, aberration, as reflected 5, 6, 9 additional mutations, respectively, detected tumors. 21/22 KRAS 18/22 regions, suggesting that they appear early have driver role (dominant trunk mutations). Branching (in EZH2, PIK3CA, TP53, exon 18) occurred two while private ABL1, ALK, BRAF, HER2, KDR, LKB1, PTEN, MET, SMAD4, SMARCB1, SRC) confined unique samples individual lesions, later on during progression. Patients showing branching ran worse clinical course, independent confounding factors. conclude exists pattern spatial temporal hierarchy dominant, branching, mutations. This consistent clonal evolution, which has potential implications patient prognosis development secondary therapy resistance.