Mutation analysis of the EGFR pathway genes, EGFR, RAS, PIK3CA, BRAF, and AKT1, in salivary gland adenoid cystic carcinoma.
Mutation analysis of the EGFR pathway genes, EGFR, RAS, PIK3CA, BRAF, and AKT1, in salivary gland adenoid cystic carcinoma.
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DOI：
10.18632/oncotarget.24818
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发表时间：
2018-03-30
期刊：
影响因子：
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通讯作者：
Inagaki H
中科院分区：
文献类型：
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作者：
Saida K;Murase T;Ito M;Fujii K;Takino H;Masaki A;Kawakita D;Ijichi K;Tada Y;Kusafuka K;Iida Y;Onitsuka T;Yatabe Y;Hanai N;Hasegawa Y;Shinomiya H;Nibu KI;Shimozato K;Inagaki H
腺样囊性癌（AdCC）是最常见的唾液腺癌之一，通常具有致命的结局。表皮生长因子受体（EGFR）通路基因突变在预测患者预后和评估靶向EGFR通路的分子治疗的疗效方面很重要。在这项唾液腺AdCC（SAdCC）研究中，我们使用高度灵敏的单碱基延伸多重检测法SNaPshot寻找EGFR、RAS家族（KRAS、HRAS和NRAS）、PIK3CA、BRAF和AKT1中的基因突变。在70例病例中，13例（18.6%）发现EGFR通路错义突变：10例（14.3%）RAS突变，1例（1.4%）EGFR突变，5例（7.1%）PIK3CA突变。通过直接测序，没有病例显示EGFR缺失。3例（4.3%）同时存在基因突变。EGFR通路突变与较短的无病生存期（p = 0.011）和总生存期（p = 0.049）显著相关，RAS突变也分别与无病生存期（p = 0.010）和总生存期（p = 0.024）显著相关。通过FISH测定确定的基因融合状态与EGFR途径中涉及的基因突变没有显著关联。总之，EGFR通路突变，尤其是RAS突变，可能在SAdCC中很常见，并且与患者的不良预后相关。
Adenoid cystic carcinoma (AdCC), one of the most common salivary gland carcinomas, usually has a fatal outcome. Epidermal growth factor receptor (EGFR) pathway gene mutations are important in predicting a patient's prognosis and estimating the efficacy of molecular therapy targeting the EGFR pathway. In this study of salivary gland AdCC (SAdCC), we looked for gene mutations in EGFR, RAS family (KRAS, HRAS, and NRAS), PIK3CA, BRAF, and AKT1, using a highly sensitive single-base extension multiplex assay, SNaPshot. Out of 70 cases, EGFR pathway missense mutations were found in 13 (18.6%): RAS mutations in 10 (14.3%), EGFR in one (1.4%), and PIK3CA in 5 (7.1%). None of the cases showed an EGFR deletion by direct sequencing. Concurrent gene mutations were found in three cases (4.3%). EGFR pathway mutations were significantly associated with a shorter disease-free (p = 0.011) and overall survival (p = 0.049) and RAS mutations were as well; (p = 0.010) and (p = 0.024), respectively. The gene fusion status as determined by a FISH assay had no significant association with mutations of the genes involved in the EGFR pathway. In conclusion, EGFR pathway mutations, especially RAS mutations, may be frequent in SAdCC, and associated with a poor prognosis for the patient.