| Title | Intratumoral Heterogeneity of ALK-Rearranged and ALK/EGFR Coaltered Lung Adenocarcinoma |
| Authors | Cai, Weijing Lin, Dongmei Wu, Chunyan Li, Xuefei Zhao, Chao Zheng, Limou Chuai, Shannon Fei, Ke Zhou, Caicun Hirsch, Fred R. |
| Affiliation | Tongji Univ, Sch Med, Shanghai Pulm Hosp, Shanghai 200433, Peoples R China. Peking Univ, Canc Hosp & Inst, Minist Educ, Key Lab Carcinogenesis & Translat Res, Beijing 100871, Peoples R China. Xiamen Univ, Xiamen, Peoples R China. Burning Rock Biotech, Guangzhou, Guangdong, Peoples R China. Univ Colorado, Ctr Canc, Aurora, CO USA. Tongji Univ, Sch Med, Inst Canc, Shanghai Pulm Hosp,Dept Med Oncol, 507 Zheng Min Rd, Shanghai 200433, Peoples R China. |
| Keywords | CHINESE PATIENTS EML4-ALK FUSION EGFR MUTATIONS ROS1 FUSIONS CANCER EVOLUTION FEATURES CARCINOMAS CRIZOTINIB |
| Issue Date | 2015 |
| Publisher | JOURNAL OF CLINICAL ONCOLOGY |
| Citation | JOURNAL OF CLINICAL ONCOLOGY.2015,33,(32),3701-+. |
| Abstract | Purpose Genetic intratumoral heterogeneity has a profound influence on the selection of clinical treatment strategies and on addressing resistance to targeted therapy. The purpose of this study was to explore the potential effect of intratumoral heterogeneity on both genetic and pathologic characteristics of ALK-rearranged lung adenocarcinoma (LADC). Methods We tested ALK fusions and EGFR mutations in 629 patients with LADC by using laser-capture microdissection to capture spatially separated tumor cell subpopulations in various adenocarcinoma subtypes and to test for ALK fusions and EGFR mutations in ALK-rearranged, EGFR-mutated, and ALK/EGFR coaltered LADCs to compare the oncogenic driver status between different tumor cell subpopulations in the same primary tumor. Results Among the 629 patients, 30 (4.8%) had ALK fusions, 364 (57.9%) had EGFR mutations, and two had ALK fusions that coexisted with EGFR mutations. Intratumoral heterogeneity of ALK fusions were identified in nine patients by reverse-transcriptase polymerase chain reaction. In the two patients with an ALK/EGFR coaltered status, genetic intratumoral heterogeneity was observed both between different growth patterns and within the same growth pattern. The relative abundance of ALK and EGFR alterations was different in the same captured area. ALK fusions were positively associated with a micropapillary pattern (P = .002) and were negatively associated with a lepidic pattern (P = .008) in an expanded statistical analysis of 900 individual adenocarcinoma components, although they appeared to be more common in acinar-predominant LADCs in the analysis of 629 patients. Conclusion Intratumoral genetic heterogeneity was demonstrated to coexist with histologic heterogeneity in both single-driver and ALK/EGFR coaltered LADCs. Altered oncogenic drivers in spatially separated subclones of the same tumor may be different. (C) 2015 by American Society of Clinical Oncology |
| URI | http://hdl.handle.net/20.500.11897/417828 |
| ISSN | 0732-183X |
| DOI | 10.1200/JCO.2014.58.8293 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 北京肿瘤医院 |
