散发性脑动静脉畸形KRAS突变及其与临床特征的关系

doi:10.3969/j.issn.1673-5765.2022.06.010

摘要/Abstract

摘要：

目的探究散发性脑动静脉畸形组织中Kirsten大鼠肉瘤病毒癌基因同源物（Kirsten rat sarcoma viral oncogene homolog，KRAS）突变与临床特征之间的关系。

方法回顾性收集散发性动静脉畸形（brain arteriovenous malformation，BAVM）术后病变组织的福尔马林固定石蜡包埋（formali n-fixation and paraffin-embedding，FFPE）样本和对应患者的临床信息，从FFPE样本中提取DNA，通过PCR扩增KRAS的指定区域（以chr12：25398284为靶点）并进行超深扩增子测序。根据是否存在KRAS突变分为突变组和无突变组，比较2组的临床特征差异。

结果本研究共纳入145例BAVM患者的FFPE样本。其中63例（43.4%）存在KRAS 体细胞突变。其中41例（28.3%）中检测到c.35G→A（G12D）突变，14例（9.7%）中检测到c.35G→T（G12V）突变。此外，还发现了几种罕见报道的KRAS突变，包括c.34G→T（G12C）突变8例（5.5%）、c.34G→A（G12S）突变7例（4.8%）、c.35G→C（G12A）突变2例（1.4%）、c.34G→C（G12R）突变1例（0.7%）。KRAS基因突变组与无突变组的临床特征差异无统计学意义。

结论本研究发现43.4%的BAVM患者存在KRAS基因突变，其中G12D是最常见的KRAS突变类型。此外，还发现了一些罕见报道的突变类型，包括G12C和G12A等。未发现KRAS突变与临床特征之间的关系

文章导读： 本研究在较大样本量FFPE处理的BAVM组织中发现KRAS突变较常见，除了既往常见的突变位点G12D和G12V外，还发现了既往少见报道的突变位点，特别是G12C和G12A，为研发靶向突变药物提供了可能的位点信息。

关键词: 脑动静脉畸形; Kirsten大鼠肉瘤病毒癌基因同源物; 突变

Abstract:

Objective To investigate the relationship between Kirsten rat sarcoma viral oncogene (KRAS) mutation in brain arteriovenous malformation (BAVM) and clinical features.

Methods The sporadic BAVM formalin-fixation and paraffin-embedding (FFPE) samples and the corresponding clinical features were collected. DNA was extracted from the BAVM FFPE samples, the specified region of KRAS (targeting chr12:25398284) was amplified by PCR and ultra-deep amplicon sequencing was performed. According to having KRAS mutation or not, the patients were divided into mutation group and no mutation group, the clinical features of the two groups were compared.

Results A total of 145 BAVM FFPE samples were collected, with 63 (43.4%) samples with KRAS somatic mutation. Of these KRAS mutations, c.35G→A(G12D) were detected in 41 samples (28.3%), and c.35G→T(G12V) in 14 samples (9.7%). In addition, several infrequent KRAS variants rarely reported were identified, including 8 cases (5.5%) with c.34G→T(G12C), 7 cases (4.8%) with c.34G→A(G12S), 2 cases (1.4%) with c.35G→C(G12A) and 1 cases (0.7%) with c.34G→C(G12R). There were no statistical differences in clinical characteristics between the KRAS mutation group and no-mutation group.

Conclusions In this study, KRAS gene mutation was found in 43.4% of BAVM patients, of which G12D was the most common mutation type of KRAS. In addition, several infrequent mutant types such as G12C and G12A were found. No relationship between KRAS mutations and clinical features were found.

Key words: Cerebral arteriovenous malformation; KRAS ; Mutation

李昊, 许宏远, 押小龙, 曹勇. 散发性脑动静脉畸形KRAS突变及其与临床特征的关系[J]. 中国卒中杂志, 2022, 17(06): 611-615.

LI Hao, XU Hongyuan, YA Xiaolong, CAO Yong. Relationship between KRAS Mutations and Clinical Features in Sporadic Brain Arteriovenous Malformations[J]. Chinese Journal of Stroke, 2022, 17(06): 611-615.

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