TY - JOUR
T1 - Comprehensive Molecular Characterization of Young Chinese Patients with Lung Adenocarcinoma Identified a Distinctive Genetic Profile
AU - Hou, Helei
AU - Zhu, Hua
AU - Zhao, Han
AU - Yan, Weihua
AU - Wang, Yongjie
AU - Jiang, Man
AU - Liu, Bin
AU - Liu, Dong
AU - Zhou, Na
AU - Zhang, Chuantao
AU - Li, Pansong
AU - Chang, Lianpeng
AU - Guan, Yanfang
AU - Wang, Zhe
AU - Zhang, Xiaoping
AU - Li, Zhuokun
AU - Fang, Bingliang
AU - Zhang, Xiaochun
N1 - Funding Information:
This work was supported by the Taishan Scholar Foundation (grant tshw201502061 to X.Z.), Qingdao People's Livelihood Science and Technology Program (grant 16-6-2-3-nsh to X.Z.), Chinese Postdoctoral Science Foundation (2017M622143 to H.H.), and Qingdao Postdoctoral Application Research Funded Project (2016052 to H.H.).
Funding Information:
This work was supported by the Taishan Scholar Foundation (grant tshw201502061 to X.Z.), Qingdao People’s Livelihood Science and Technology Program (grant 16-6-2-3-nsh to X.Z.), Chinese Postdoctoral Science Foundation (2017M622143 to H.H.), and Qingdao Postdoctoral Application Research Funded Project (2016052 to H.H.).
Publisher Copyright:
© AlphaMed Press 2018
PY - 2018/9
Y1 - 2018/9
N2 - Background: Occurrence at a younger age has been demonstrated to be associated with a distinct biology in non-small cell lung cancer. However, genomics and clinical characteristics among younger patients with lung adenocarcinoma remain to be determined. Here we studied the potentially targetable genetic alterations by next-generation sequencing (NGS) assay in young Chinese patients with lung adenocarcinoma. Materials and Methods: Seventy-one surgically resected lung adenocarcinoma tissue samples from patients aged less than 45 years were collected with informed consent from all patients. Targeted NGS assays were used to identify actionable genetic alterations in the cancer tissues. Additionally, the genomic and clinicopathologic characteristics of 106 patients with lung adenocarcinoma who received NGS testing over the same period were analyzed retrospectively. Results: The frequencies of targetable genetic alterations in 177 patients with lung adenocarcinoma were analyzed by defined age categories, which unveiled a distinctive molecular profile in the younger group, aged less than 45 years. Notably, higher frequency of ALK and HER2 genetic alterations were associated with young age. However, a reverse trend was observed for KRAS, STK11 and EGFR exon 20 mutations, which were more frequently identified in the older group, aged more than 46 years. Furthermore, concurrent EGFR/TP53 mutations were much more prevalent in the younger patients (81.6% vs. 46.8%), which might have a poor response to treatment with epidermal growth factor receptor tyrosine kinase inhibitor. Conclusion: In this study, NGS assay revealed a distinctive genetic profile in younger patients with adenocarcinoma. High frequency of concurrent EGFR/TP53 mutations was found in the younger patients, which especially warranted personalized treatment in this population. Implications for Practice: Further investigation is needed to understand the genomics and clinical characteristics of young patients with lung adenocarcinoma. In the present study, hybrid capture-based next-generation sequencing assays were used to identify targeted genetic alterations in young lung adenocarcinoma patients. Young patients with lung adenocarcinoma, aged less than 45 years, harbored a higher frequency of ALK and HER2 genetic alterations compared with patients aged more than 46 years. Dramatically, concurrent EGFR/TP53 mutations were much more prevalent in younger patients, which had a poor response to treatment with epidermal growth factor receptor kinase inhibitor. These results reveal a distinctive genetic profile in younger patients with adenocarcinoma, which might improve the treatment of this subpopulation.
AB - Background: Occurrence at a younger age has been demonstrated to be associated with a distinct biology in non-small cell lung cancer. However, genomics and clinical characteristics among younger patients with lung adenocarcinoma remain to be determined. Here we studied the potentially targetable genetic alterations by next-generation sequencing (NGS) assay in young Chinese patients with lung adenocarcinoma. Materials and Methods: Seventy-one surgically resected lung adenocarcinoma tissue samples from patients aged less than 45 years were collected with informed consent from all patients. Targeted NGS assays were used to identify actionable genetic alterations in the cancer tissues. Additionally, the genomic and clinicopathologic characteristics of 106 patients with lung adenocarcinoma who received NGS testing over the same period were analyzed retrospectively. Results: The frequencies of targetable genetic alterations in 177 patients with lung adenocarcinoma were analyzed by defined age categories, which unveiled a distinctive molecular profile in the younger group, aged less than 45 years. Notably, higher frequency of ALK and HER2 genetic alterations were associated with young age. However, a reverse trend was observed for KRAS, STK11 and EGFR exon 20 mutations, which were more frequently identified in the older group, aged more than 46 years. Furthermore, concurrent EGFR/TP53 mutations were much more prevalent in the younger patients (81.6% vs. 46.8%), which might have a poor response to treatment with epidermal growth factor receptor tyrosine kinase inhibitor. Conclusion: In this study, NGS assay revealed a distinctive genetic profile in younger patients with adenocarcinoma. High frequency of concurrent EGFR/TP53 mutations was found in the younger patients, which especially warranted personalized treatment in this population. Implications for Practice: Further investigation is needed to understand the genomics and clinical characteristics of young patients with lung adenocarcinoma. In the present study, hybrid capture-based next-generation sequencing assays were used to identify targeted genetic alterations in young lung adenocarcinoma patients. Young patients with lung adenocarcinoma, aged less than 45 years, harbored a higher frequency of ALK and HER2 genetic alterations compared with patients aged more than 46 years. Dramatically, concurrent EGFR/TP53 mutations were much more prevalent in younger patients, which had a poor response to treatment with epidermal growth factor receptor kinase inhibitor. These results reveal a distinctive genetic profile in younger patients with adenocarcinoma, which might improve the treatment of this subpopulation.
KW - Genetic profile
KW - Lung adenocarcinoma
KW - Next-generation sequencing
KW - Young age
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U2 - 10.1634/theoncologist.2017-0629
DO - 10.1634/theoncologist.2017-0629
M3 - Article
C2 - 29700208
AN - SCOPUS:85046025361
SN - 1083-7159
VL - 23
SP - 1008
EP - 1015
JO - Oncologist
JF - Oncologist
IS - 9
ER -