Department of Gynecological Oncology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200082, China.
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Genes (Basel). 2022 Jan 31;13(2):287. doi: 10.3390/genes13020287.
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.
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，但宫颈癌的遗传特征仍有待充分阐明，尤其是在亚洲人群中。在此，我们使用经过验证的多基因下一代测序（NGS）面板研究了中国宫颈癌患者的遗传特征。我们通过对 32 名中国宫颈癌患者的 32 个肿瘤和 32 个血液样本进行多基因 NGS 分析，使用靶向 571 个癌症相关基因的面板来分析基因图谱。共鉴定出 810 个体细胞变异、2730 个种系突变和 701 个拷贝数变异（CNV）。FAT1、HLA-B、PIK3CA、MTOR、KMT2D 和 ZFHX3 是突变最多的基因。此外，PIK3CA、BRCA1、BRCA2、ATM 和 TP53 基因座的 CNV 频率更高。此外，通过与 ONCOKB 数据库进行比较，进一步强调了 PIK3CA 在宫颈癌中的作用，尤其是 E545K 和 E542K，它们被报道赋予宫颈癌放射抗性。值得注意的是，对潜在治疗靶点的分析表明，PARP 抑制剂可能使宫颈癌患者受益。这项多基因 NGS 分析揭示了中国宫颈癌患者的一些新的遗传改变，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，还影响宫颈癌对放疗的耐药性，但需要进一步开展涉及更大患者群体的研究来验证这些发现。
