Testicular germ cell tumor (TGCT) development may involve a series of modification at epigenetic and genetic level which may act synergistically and transform the primordial gonocyte. This study evaluated the frequency and distribution pattern of RASSF1A/MGMT gene methylation and KRAS, BRAF and cKIT gene mutation in Indian TGCT patient, and their correlation with clinicopathological features. Forty-one TGCT tumors were used to investigate hypermethylation of RASSF1A and MGMT gene and mutations of KRAS codon 12/13, BRAF V600E and cKIT exon 17 mutations. RASSF1A and MGMT methylation was noted in 58.5% and 10% of the TGCTs. A higher frequency of RASSF1A methylation was noted in seminomas (71%, 17/24), while MGMT methylation was frequent in mixed tumors (23%, 3/13). Interestingly, 3 of 41 cases showed concurrent methylation of both the genes. The absence of tumor necrosis was significantly associated with increased frequency of MGMT hypermethylation (30% vs. 3%, p = 0.03). KRAS mutation was identified in 17% (7/41), while none showed BRAF and cKIT mutation. KRAS mutations were predominantly found in codon 12 with G12V as the most recurrent mutations. Mixed germ tumors tends to show increased frequency of KRAS mutation (31%, 4/13), followed by pure seminomas (4%, 1/24). Interestingly, KRAS mutation rate was significantly higher in metastatic tumors in comparison to primary tumors (100% vs. 13%, p = 0.02). No other association of RASSF1A/MGMT/KRAS alterations with other clinicopathological features was noted. In conclusion, these data support the notion that the cancer-associated alterations in the RASSF1, MGMT and KRAS gene may significantly contribute to TGCT pathogenesis.

睾丸生殖细胞肿瘤（TGCT）的发展可能涉及表观遗传和遗传水平的一系列修饰，这些修饰可以协同作用并转化原始生殖细胞。本研究评估了印度TGCT患者RASSF1A / MGMT基因甲基化的频率和分布模式以及KRAS，BRAF和cKIT基因突变及其与临床病理特征的关系。41例TGCT肿瘤用于研究RASSF1A和MGMT基因的超甲基化以及KRAS密码子12/13，BRAF V600E和cKIT外显子17突变的突变。RASSF1A和在58.5％和10％的TGCT中发现了MGMT甲基化。在精原细胞瘤中，RASSF1A甲基化的频率更高（71％，17/24），而在混合肿瘤中MGMT甲基化频繁（23％，3/13）。有趣的是，41例病例中有3例同时显示两个基因的甲基化。肿瘤坏死的缺乏与MGMT高甲基化频率的增加显着相关（30％比3％，p  = 0.03）。在17％（7/41）中发现了KRAS突变，而没有人显示出BRAF和cKIT突变。卡拉斯突变主要在12号密码子中发现，其中G12V是最常见的突变。混合性生殖肿瘤倾向于表现出增加的KRAS突变频率（31％，4/13），其次是单纯的精原细胞瘤（4％，1/24）。有趣的是，与原发性肿瘤相比，转移性肿瘤中的KRAS突变率显着更高（100％比13％，p  = 0.02）。没有其他RASSF1A / MGMT / KRAS改变与其他临床病理特征的关联。总之，这些数据支持以下观念：RASSF1，MGMT和KRAS基因中与癌症相关的改变可能显着促成TGCT发病机理。