子宫颈透明细胞腺癌（CCAC）是一种特殊的HPV独立型子宫颈癌。它的发病率较低，早期诊断困难，预后不良。在青春期达到高峰，对女性健康构成巨大威胁。因此，研究子宫颈透明细胞腺癌的发病机制，以指导后续的治疗和预防工作非常重要。本研究分析了郑州大学第一附属医院三名被诊断为CCAC的青少年患者。采用下一代测序方法，通过分析患者的遗传变异，研究了其发病机制以及与患者亲属的相关性。发现CMTM5是唯一的共同突变基因。通过文献研究和相关疾病致病基因的比较分析，筛选出19个基因中的6个基因（ALKBH7，MYCBP，MZF1，RNF207，RRS1和TUSC2）在患者中存在突变，并且在生殖癌中具有较高的突变率。途径分析显示，与非HPV子宫颈癌相关的下调基因主要与免疫系统反应有关，表明非HPV子宫颈癌与HPV感染的子宫颈癌不同，免疫反应较弱，与病毒感染的相关性较低，这与病毒感染的特点一致。版权所有2023年Su，Zhang，Zhou，Zhang，Chen，Zhang，Wang，Zhang，Zhang，Li，Zhang，Wang，Yuan，Zhang，Zhou，Cao，Zhang和Luo.

Clear cell adenocarcinoma of the cervix (CCAC) is a special type of HPV-independent cervical cancer. It has a low incidence rate, can be difficult to diagnose early, has a poor prognosis. Its peak incidence is in adolescence, which poses a great threat to women's health. Therefore, it is very important to explore the pathogenesis of cervical clear cell adenocarcinoma to guide subsequent treatment and prevention. This study analyzed 3 juvenile patients with CCAC diagnosed at the First Affiliated Hospital of Zhengzhou University. Using next-generation sequencing methods, we analyzed the pathogenesis of the patients and their close relatives by analyzing the genetic alterations of patients. CMTM5 was identified as the only shared mutated gene. Using published literature and comparative analyses of related disease-causing genes, 6 of the 19 genes (ALKBH7, MYCBP, MZF1, RNF207, RRS1, and TUSC2) were screened as genes with mutations in patients and had higher mutation rates in reproductive cancers. Pathway analysis showed that downregulated genes in non-HPV cervical cancer were mainly related to the immune system response, suggesting that non-HPV cervical cancer differs from HPV-infected cervical cancer in that the immune response is weaker, which is consistent with the weak correlation with viral infection.Copyright © 2023 Su, Zhang, Zhou, Zhang, Chen, Zhang, Wang, Zhang, Zhang, Li, Zhang, Wang, Yuan, Zhang, Zhou, Cao, Zhang and Luo.