宫颈癌是全球女性癌症相关死亡的第四大原因。尽管已经进行了许多测序研究,宫颈癌的遗传特征仍有待充分阐明,尤其是亚洲人口。在这里,我们使用经过验证的多基因下一代测序(NGS)小组调查了中国宫颈癌患者的遗传格局.我们分析了64个样本,由来自32名中国宫颈癌患者的32个肿瘤和32个血液样本组成,通过对571个癌症相关基因进行多基因NGS。共有810个体细胞变异,鉴定了2730种系突变和701个拷贝数变异(CNV)。FAT1,HLA-B,PIK3CA,MTOR,KMT2D和ZFHX3是突变最多的基因。Further,PIK3CA,BRCA1、BRCA2、ATM和TP53基因位点具有较高的CNVs发生频率。此外,通过与ONCOKB数据库的比较,进一步强调了PIK3CA在宫颈癌中的作用,尤其是E545K和E542K,据报道,这对宫颈癌具有放射抗性。值得注意的是,对潜在治疗靶点的分析表明,宫颈癌患者可以从PARP抑制剂中获益.这种多基因NGS分析揭示了中国宫颈癌患者的几种新的遗传改变,并强调了PIK3CA在宫颈癌中的作用。总的来说,这项研究表明,遗传变异不仅影响宫颈癌的遗传易感性,还会影响宫颈癌对放疗的抵抗力,但应该开展更多患者人群的进一步研究来验证这些发现.
Cervical cancer is the fourth leading cause of cancer-related deaths in women worldwide. Although many sequencing studies have been carried out, the genetic characteristics of cervical cancer remain to be fully elucidated, especially in the Asian population. Herein, we investigated the genetic landscape of Chinese cervical cancer patients using a validated multigene next generation sequencing (NGS) panel. We analyzed 64 samples, consisting of 32 tumors and 32 blood samples from 32 Chinese cervical cancer patients by performing multigene NGS with a panel targeting 571 cancer-related genes. A total of 810 somatic variants, 2730 germline mutations and 701 copy number variations (CNVs) were identified. FAT1, HLA-B, PIK3CA, MTOR, KMT2D and ZFHX3 were the most mutated genes. Further, PIK3CA, BRCA1, BRCA2, ATM and TP53 gene loci had a higher frequency of CNVs. Moreover, the role of PIK3CA in cervical cancer was further highlighted by comparing with the ONCOKB database, especially for E545K and E542K, which were reported to confer radioresistance to cervical cancer. Notably, analysis of potential therapeutic targets suggested that cervical cancer patients could benefit from PARP inhibitors. This multigene NGS analysis revealed several novel genetic alterations in Chinese patients with cervical cancer and highlighted the role of PIK3CA in cervical cancer. Overall, this study showed that genetic variations not only affect the genetic susceptibility of cervical cancer, but also influence the resistance of cervical cancer to radiotherapy, but further studies involving a larger patient population should be undertaken to validate these findings.