Carlos-Escalante José Alberto, Mejía-Pérez Sonia Iliana, Soto-Reyes Ernesto, Guerra-Calderas Lissania, Cacho-Díaz Bernardo, Torres-Arciga Karla, Montalvo-Casimiro Michel, González-Barrios Rodrigo, Reynoso-Noverón Nancy, Ruiz-de la Cruz Miguel, Díaz-Velásquez Clara Estela, Vidal-Millán Silvia, Álvarez-Gómez Rosa María, Sánchez-Correa Thalía Estefanía, Pech-Cervantes Claudio Hiram, Soria-Lucio José Antonio, Pérez-Castillo Areli, Salazar Ana María, Arriaga-Canon Cristian, Vaca-Paniagua Felipe, González-Arenas Aliesha, Ostrosky-Wegman Patricia, Mohar-Betancourt Alejandro, Herrera Luis A, Corona Teresa, Wegman-Ostrosky Talia
PECEM (MD/PhD), Facultad de Medicina, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico.
Departamento de Enseñanza, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", 14269, Mexico City, Mexico.
J Neurooncol. 2023 Jan;161(1):165-174. doi: 10.1007/s11060-022-04214-1. Epub 2022 Dec 16.
Astrocytomas are a type of malignant brain tumor with an unfavorable clinical course. The impact of AGT and MGMT somatic variants in the prognosis of astrocytoma is unknown, and it is controversial for TP53. Moreover, there is a lack of knowledge regarding the molecular characteristics of astrocytomas in Mexican patients.
We studied 48 Mexican patients, men and women, with astrocytoma (discovery cohort). We performed DNA deep sequencing in tumor samples, targeting AGT, MGMT and TP53, and we studied MGMT gene promoter methylation status. Then we compared our findings to a cohort which included data from patients with astrocytoma from The Cancer Genome Atlas (validation cohort).
In the discovery cohort, we found a higher number of somatic variants in AGT and MGMT than in the validation cohort (10.4% vs < 1%, p < 0.001), and, in both cohorts, we observed only women carried variants AGT variants. We also found that the presence of either MGMT variant or promoter methylation was associated to better survival and response to chemotherapy, and, in conjunction with TP53 variants, to progression-free survival.
The occurrence of AGT variants only in women expands our knowledge about the molecular differences in astrocytoma between men and women. The increased prevalence of AGT and MGMT variants in the discovery cohort also points towards possible distinctions in the molecular landscape of astrocytoma among populations. Our findings warrant further study.
星形细胞瘤是一种临床病程不佳的恶性脑肿瘤。AGT和MGMT体细胞变异对星形细胞瘤预后的影响尚不清楚，TP53的情况存在争议。此外，对于墨西哥患者星形细胞瘤的分子特征了解不足。
我们研究了48名患有星形细胞瘤的墨西哥患者（发现队列），男女均有。我们对肿瘤样本进行DNA深度测序，检测AGT、MGMT和TP53，并研究MGMT基因启动子甲基化状态。然后我们将研究结果与一个队列进行比较，该队列包含来自癌症基因组图谱的星形细胞瘤患者数据（验证队列）。
在发现队列中，我们发现AGT和MGMT中的体细胞变异数量高于验证队列（10.4%对<1%，p<0.001），并且在两个队列中，我们观察到只有女性携带AGT变异。我们还发现，MGMT变异或启动子甲基化的存在与更好的生存率和化疗反应相关，并且与TP53变异一起，与无进展生存期相关。
仅在女性中出现AGT变异扩展了我们对男女星形细胞瘤分子差异的认识。发现队列中AGT和MGMT变异患病率的增加也表明不同人群中星形细胞瘤分子格局可能存在差异。我们的发现值得进一步研究。
