Department of Medical Oncology, Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, People's Republic of China.
Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, People's Republic of China.
Oncologist. 2018 Sep;23(9):1008-1015. doi: 10.1634/theoncologist.2017-0629. Epub 2018 Apr 26.
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.
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.
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 and genetic alterations were associated with young age. However, a reverse trend was observed for , and exon 20 mutations, which were more frequently identified in the older group, aged more than 46 years. Furthermore, concurrent / 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.
In this study, NGS assay revealed a distinctive genetic profile in younger patients with adenocarcinoma. High frequency of concurrent / mutations was found in the younger patients, which especially warranted personalized treatment in this population.
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 and genetic alterations compared with patients aged more than 46 years. Dramatically, concurrent / 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.
非小细胞肺癌的研究表明，发病年龄较小与独特的生物学特征相关。然而，年轻的肺腺癌患者的基因组学和临床特征仍有待确定。在这里，我们通过下一代测序（NGS）检测研究了年轻的中国肺腺癌患者的潜在靶向遗传改变。
本研究经所有患者知情同意后，收集了 71 例年龄小于 45 岁的肺腺癌患者的手术切除组织样本。使用靶向 NGS 检测方法来鉴定癌症组织中的可靶向遗传改变。此外，还回顾性分析了同期接受 NGS 检测的 106 例肺腺癌患者的基因组学和临床病理特征。
通过年龄分类分析了 177 例肺腺癌患者的可靶向遗传改变频率，揭示了年轻组（<45 岁）的独特分子谱。值得注意的是， 、 基因突变的频率与年龄较小相关。然而，对于 、 以及外显子 20 突变，情况则相反，其在年龄较大的组（>46 岁）中更为常见。此外，年轻患者（81.6%比 46.8%）中更常见同时存在 / 突变，这可能对表皮生长因子受体酪氨酸激酶抑制剂的治疗反应较差。
在这项研究中，NGS 检测揭示了腺癌年轻患者的独特遗传特征。在年轻患者中发现了高频的同时存在 / 突变，这尤其需要对这一人群进行个性化治疗。
需要进一步研究以了解年轻肺腺癌患者的基因组学和临床特征。在本研究中，使用杂交捕获的下一代测序检测方法来鉴定年轻肺腺癌患者的靶向遗传改变。年龄小于 45 岁的肺腺癌患者与年龄大于 46 岁的患者相比，携带 、 基因突变的频率更高。更为显著的是，年轻患者中同时存在 / 突变更为常见，对表皮生长因子受体激酶抑制剂的治疗反应较差。这些结果揭示了年轻腺癌患者的独特遗传特征，这可能改善对这一亚群的治疗。
