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6595例肺癌中表皮生长因子受体(EGFR)、 Kirsten大鼠肉瘤病毒癌基因(KRAS)和间变性淋巴瘤激酶(ALK)改变的临床病理特征

Clinicopathologic characteristics of EGFR, KRAS, and ALK alterations in 6,595 lung cancers.

作者信息

Lee Boram, Lee Taebum, Lee Se-Hoon, Choi Yoon La, Han Joungho

机构信息

Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.

出版信息

Oncotarget. 2016 Apr 26;7(17):23874-84. doi: 10.18632/oncotarget.8074.

Abstract

BACKGROUND

EGFR, KRAS, and ALK alterations are major genetic changes found in non-small cell lung cancers (NSCLCs). Testing advanced lung adenocarcinoma tumors for these three genes is now standard care. The purpose of this study was to investigate the clinicopathologic expression pattern of these three genes in East Asian NSCLC patients.

PATIENTS AND METHODS

We conducted a retrospective study of all patients tested for mutations of these three genes at a single institute in Korea between 2006 and 2014. Study data were extracted from electronic medical records. Univariate and multivariate logistic regression analyses were used to measure associations between clinicopathologic features and alterations of EGFR, KRAS, and ALK.

RESULTS

We detected 12 EGFR-mutated tumors with additional mutations in KRAS (N=6, 0.1%) or ALK (N=6, 0.1%). General clinicopathologic characteristics of tumors with EGFR, KRAS, or ALK mutations were similar to previous reports. Patients having EGFR L858R point mutations were older than patients having EGFR exon 19 deletions. EGFR G719X point mutations were more common in men and smokers than exon 19 deletions or L858R point mutations. Tumors having KRAS G12C mutations were less often of mucinous type than those with G12D or G12V, mutations.

CONCLUSIONS

This is the largest three gene molecular epidemiology study in East Asian NSCLC patients. Each genetic alteration was associated with distinct clinicopathologic characteristics. Furthermore, different age and sex are associated with different subtypes of EGFR and KRAS mutations.

摘要

背景

表皮生长因子受体(EGFR)、 Kirsten 大鼠肉瘤病毒癌基因(KRAS)和间变性淋巴瘤激酶(ALK)改变是在非小细胞肺癌(NSCLC)中发现的主要基因变化。检测晚期肺腺癌肿瘤中的这三个基因现在是标准治疗方法。本研究的目的是调查这三个基因在东亚 NSCLC 患者中的临床病理表达模式。

患者与方法

我们对 2006 年至 2014 年期间在韩国一家机构接受这三个基因检测的所有患者进行了回顾性研究。研究数据从电子病历中提取。采用单因素和多因素逻辑回归分析来衡量临床病理特征与 EGFR、KRAS 和 ALK 改变之间的关联。

结果

我们检测到 12 例 EGFR 突变肿瘤,伴有 KRAS(n = 6,0.1%)或 ALK(n = 6,0.1%)的额外突变。具有 EGFR、KRAS 或 ALK 突变的肿瘤的一般临床病理特征与先前报道相似。具有 EGFR L858R 点突变的患者比具有 EGFR 外显子 19 缺失的患者年龄更大。EGFR G719X 点突变在男性和吸烟者中比外显子 19 缺失或 L858R 点突变更常见。具有 KRAS G12C 突变的肿瘤比具有 G12D 或 G12V 突变的肿瘤黏液型更少。

结论

这是东亚 NSCLC 患者中最大的三项基因分子流行病学研究。每种基因改变都与不同的临床病理特征相关。此外,不同的年龄和性别与 EGFR 和 KRAS 突变的不同亚型相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e5a/5029670/af120bdf20b8/oncotarget-07-23874-g001.jpg

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