Whole-Exome Sequencing of Salivary Gland Mucoepidermoid Carcinoma.
Whole-Exome Sequencing of Salivary Gland Mucoepidermoid Carcinoma.
复制标题
DOI：
10.1158/1078-0432.ccr-16-0720
复制
发表时间：
2017-01-01
期刊：
影响因子：
--
通讯作者：
Agrawal N
中科院分区：
文献类型：
--
作者：
Kang H;Tan M;Bishop JA;Jones S;Sausen M;Ha PK;Agrawal N
黏液表皮样癌是最常见的唾液腺恶性肿瘤。为了探索MEC的遗传起源，我们对这些肿瘤进行了系统的基因组分析。对18例具有匹配正常组织的原发癌进行了全外显子组测序和基因拷贝数分析。采用荧光原位杂交法（FISH）测定17例肿瘤中MECT1-MAML2易位的存在与否。TP53是MEC中最常见的突变基因（28%），仅在中级和高级肿瘤中发现突变。总的来说，TP53突变的肿瘤比没有TP53突变的肿瘤有更多的突变（p=0.006）。POU6F2是第二常见的突变基因，在三个具有相同框内缺失的低级别mec中发现。IRAK1、MAP3K9、ITGAL、ERBB4、OTOGL、KMT2C和obn的体细胞改变在18个测序的肿瘤中至少有两个被鉴定出来。FISH分析证实17例肿瘤中有15例（88%）存在MECT1-MAML2易位。通过这些整合的基因组分析，MECT1-MAML2易位和体细胞TP53和POU6F2突变似乎是粘液表皮样癌的主要驱动因素。
Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. To explore the genetic origins of MEC, we performed systematic genomic analyses of these tumors. Whole-exome sequencing and gene copy number analyses were performed for 18 primary cancers with matched normal tissue. Fluorescence in situ hybridization (FISH) was used to determine the presence or absence of the MECT1-MAML2 translocation in 17 tumors. TP53 was the most commonly mutated gene in MEC (28%), and mutations were found only in intermediate- and high-grade tumors. Tumors with TP53 mutations had more mutations overall than tumors without TP53 mutations (p=0.006). POU6F2 was the second most frequently mutated gene, found in three low-grade MECs with the same in-frame deletion. Somatic alterations in IRAK1, MAP3K9, ITGAL, ERBB4, OTOGL, KMT2C, and OBSCN were identified in at least two of the 18 tumors sequenced. FISH analysis confirmed the presence of the MECT1-MAML2 translocation in 15 of 17 tumors (88%). Through these integrated genomic analyses, MECT1-MAML2 translocation and somatic TP53 and POU6F2 mutations appear to be the main drivers of mucoepidermoid carcinoma.