中国年轻肺腺癌患者基因特点研究  

Genetic Profile of Young Chinese Patients with Lung Adenocarcinoma

作　　者：梁宇[1] 侯和磊[1] 姜曼[1] 张传涛 刘栋[1] 张晓春[1] Yu LIANG;Helei HOU;Man JIANG;Chuantao ZHANG;Dong LIU;Xiaochun ZHANG(Department of Medical Oncology,The Affiliated Hospital of Qingdao University,Qingdao 266003,China)

机构地区：[1]青岛大学附属医院肿瘤科,青岛266003

出　　处：《中国肺癌杂志》2020年第4期239-246,共8页Chinese Journal of Lung Cancer

摘　　要：背景与目的全球肺癌的发病率正呈逐年上升趋势,其中腺癌所占的百分比日益升高。据统计,全球的肺癌平均初诊年龄在70岁左右,虽然肺癌仍以老年患者居多,但发病年龄的年轻化趋势愈加明显。结合现有研究数据,我们已知在非小细胞肺癌中,年轻患者疾病的发生有其独特的生物学特点。但年轻肺腺癌患者的基因组学特性和临床特征仍有待确定。本研究采用高通量测序(next-generation sequencing technology,NGS)技术对中国年轻肺腺癌患者的基因突变状态进行了研究。方法共收集了89例年龄≤45岁的肺腺癌患者组织标本,所有患者均知情同意。使用NGS检测用于确定癌组织中驱动基因突变。此外,对同期行NGS检测的95例>45岁肺腺癌患者的基因组和临床病理特征进行回顾性分析。结果根据年龄分类对184例肺腺癌患者的驱动基因突变频率进行了分析,揭示了年龄≤45岁的年轻组患者的独特基因特征。其中间变淋巴瘤激酶(anaplastic lymphoma kinase,ALK)融合基因和人表皮生长因子受体-2(human epidermal growth factor receptor 2,HER2)基因的突变频率较高。而鼠类肉瘤病毒癌基因(kirsten rat sarcoma viral oncogene,KRAS)、丝氨酸/苏氨酸蛋白激酶11(serine/threonine kinase 11,STK11)和表皮生长因子受体(epidermal growth factor receptor,EGFR)20外显子突变的趋势则相反,这些突变在年龄>45岁的老年组中更为常见。此外,年轻组EGFR基因突变同时伴有肿瘤蛋白p53(tumor protein p53,TP53)基因突变较老年组更为普遍(81.6%vs 44.9%),这可能使其应用EGFR酪氨酸激酶抑制剂(EGFR-tyrosine kinase inhibitor,EGFR-TKI)后疗效较差。结论NGS分析显示年轻腺癌患者具有独特的基因突变特点。在年轻患者中发现EGFR/TP53共突变的频率较高,这些独特的基因组学特征对临床治疗有重要的指导意义。Background and objective 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.Methods Eighty-nine 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 clinical pathologic characteristics of 95 patients with lung adenocarcinoma who received NGS testing over the same period were analyzed retrospectively.Results The frequencies of targetable genetic alterations in 184 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 anaplastic lymphoma kinase(ALK)and human epidermal growth factor receptor 2(HER2)genetic alterations were associated with young age.However,a reverse trend was observed for kirsten rat sarcoma viral oncogene(KRAS),serine/threonine kinase 11(STK11)and epidermal growth factor receptor(EGFR)exon 20 mutations,which were more frequently identified in the older group,aged more than 45 years.Furthermore,concurrent EGFR/tumor protein p53(TP53)mutations were much more prevalent in the younger patients(81.6%vs 44.9%),which might have a poor response to treatment with EGFR-tyrosine kinase inhibitor(EGFR-TKI).Conclusion 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.

关 键 词：肺腺癌 年轻 高通量测序 基因图谱 

分 类 号：R734.2[医药卫生—肿瘤]