Bell Diana, Sniegowski Matthew C, Wani Khalida, Prieto Victor, Esmaeli Bita
Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas.
Orbital Oncology and Ophthalmic Plastic Surgery Program, Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Head Neck. 2016 Apr;38 Suppl 1(Suppl 1):E724-E729. doi: 10.1002/hed.24078. Epub 2015 Jun 15.
Lacrimal gland carcinomas are rare. Identification of molecular abnormalities underlying lacrimal gland carcinogenesis is critical to the development of new targeted therapies for lacrimal gland carcinomas. The purpose of our study was to look for mutations that can be targeted as new treatments for lacrimal gland carcinomas.
Genomic DNA from patients with lacrimal gland epithelial neoplasms was analyzed. The Sequenom matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass ARRAY platform was used to profile 168 common oncogenic point mutations in 40 genes. Mutation frequency was assessed overall and by histologic diagnosis. These genetic mutations were then correlated with clinical outcomes in the patients.
The study included 14 men and 10 women with a median age of 45 years (range, 17-75 years). The histologic diagnoses were as follows: adenoid cystic carcinoma (n = 16), low-grade carcinoma ex pleomorphic adenoma (n = 2), high-grade carcinoma ex pleomorphic adenoma (n = 2), squamous carcinoma (n = 1), and pleomorphic adenoma (n = 3). Analysis revealed 18 oncogenic mutations in 13 patients: KRAS mutations in 10 patients (46%), NRAS mutations in 2 patients (8%), MET mutations in 3 patients (13%), PIK3CA mutation in 1 patient (4%), and BRAF mutation in no patients. About half of the patients with adenoid cystic carcinoma had oncogenic mutations (7 of 16; 44%). Of the 16 patients with adenoid cystic carcinoma, 5 had KRAS mutations, 1 had MET mutations, and 1 had an NRAS mutation.
KRAS, NRAS, and MET mutations are frequent in epithelial neoplasms of the lacrimal gland, with the highest rate of mutations found in adenoid cystic carcinoma. Therapies targeting these genes may be effective treatments for lacrimal gland carcinomas. © 2015 Wiley Periodicals, Head Neck 38: E-E, 2016.
泪腺癌较为罕见。确定泪腺癌发生的分子异常对于开发针对泪腺癌的新靶向治疗至关重要。我们研究的目的是寻找可作为泪腺癌新治疗靶点的突变。
对泪腺上皮性肿瘤患者的基因组DNA进行分析。使用Sequenom基质辅助激光解吸电离飞行时间（MALDI-TOF）质谱阵列平台对40个基因中的168个常见致癌点突变进行分析。总体及按组织学诊断评估突变频率。然后将这些基因突变与患者的临床结局相关联。
该研究纳入了14名男性和10名女性，中位年龄为45岁（范围17 - 75岁）。组织学诊断如下：腺样囊性癌（n = 16）、低度恶性多形性腺瘤癌变（n = 2）、高度恶性多形性腺瘤癌变（n = 2）、鳞状细胞癌（n = 1）和多形性腺瘤（n = 3）。分析发现13名患者中有18个致癌突变：10名患者（46%）存在KRAS突变，2名患者（8%）存在NRAS突变，3名患者（13%）存在MET突变，1名患者（4%）存在PIK3CA突变，无患者存在BRAF突变。约一半的腺样囊性癌患者存在致癌突变（16例中的7例；44%）。在16例腺样囊性癌患者中，5例存在KRAS突变，1例存在MET突变，1例存在NRAS突变。
KRAS、NRAS和MET突变在泪腺上皮性肿瘤中较为常见，其中腺样囊性癌的突变率最高。针对这些基因的治疗可能是泪腺癌的有效治疗方法。© 2015威利期刊公司，《头颈》38：E - E，2016。
