Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
Hum Gene Ther. 2020 Aug;31(15-16):881-890. doi: 10.1089/hum.2019.305. Epub 2020 Mar 27.
The aim is to investigate the genomic characterization of uterine sarcoma for rAd- (Gendicine) combined with chemotherapy treatment. We recently published an article on 12 cases of uterine sarcomas, which were treated with rAd- combined with chemotherapy. We found that rAd- combined with chemotherapy is effective for various uterine sarcomas. Pretreatment pathological specimens of four uterine sarcoma patients were collected from the above recent clinical research and numbered 1-4A/B. Tumor samples were subjected to targeted sequencing by using a 416 genes panel. We profiled the mutation spectrum and tumor mutation burden in the tumors, identified mutated genes, and explored their gene function. We also verified the p53 protein expression using immunohistochemistry. We identified a total of 30 mutated genes that were found from the next-generation sequencing test results. The average number of mutated genes was up to seven in the five samples. gene was mutated in two of the four patients, No. 1 and No. 4B. They are c.C833G (p.P278R) missense mutation and a point mutation (C141*) that result in a premature stop codon. We did not find a mutated gene in the other two cases, but we identified mutated genes, including , , , and which were located upstream of the gene; they may have an impact on . We also identified 11 additional genes which are involved in -related signaling pathways or have interaction with p53. Compared to solid tumor mutational burden (TMB) distribution, none of their TMB was ranking in the top 25%. Mutant p53 protein expression was positive in two specimens. Our results demonstrated that the signaling pathway plays an important role in uterine sarcoma tumorigenesis. and the upstream genes such as , , , and may be involved in the genomic characterization for rAd- (Gendicine) combined with chemotherapy in uterine sarcoma. Besides, the average amount of mutated genes from every patient is large.
目的是研究子宫肉瘤的基因组特征，以便进行 rAd-（Gendicine）联合化疗治疗。我们最近发表了一篇关于 12 例子宫肉瘤患者的文章，这些患者接受了 rAd-联合化疗治疗。我们发现 rAd-联合化疗对各种子宫肉瘤均有效。从上述最近的临床研究中收集了 4 例子宫肉瘤患者的 4 份预处理病理标本，编号为 1-4A/B。使用 416 个基因面板对肿瘤样本进行靶向测序。我们对肿瘤中的突变谱和肿瘤突变负担进行了分析，鉴定了突变基因，并探讨了它们的基因功能。我们还使用免疫组织化学法验证了 p53 蛋白的表达。从下一代测序测试结果中总共鉴定出 30 个突变基因。在这 5 个样本中，平均每个样本有多达 7 个基因突变。在 4 个患者中的 2 个（1 号和 4B 号）中发现了 基因发生突变，分别为 c.C833G（p.P278R）错义突变和导致提前终止密码子的点突变（C141*）。在另外 2 个病例中，我们没有发现突变的 基因，但我们鉴定了突变基因，包括 、 、 、 ，它们位于 基因的上游；它们可能对 有影响。我们还鉴定了 11 个额外的基因，这些基因参与 -相关信号通路或与 p53 相互作用。与实体瘤突变负担（TMB）分布相比，它们的 TMB 均未进入前 25%。在 2 个标本中检测到突变型 p53 蛋白表达阳性。我们的结果表明， 信号通路在子宫肉瘤肿瘤发生中起重要作用。 以及 、 、 等上游基因可能参与了 rAd-（Gendicine）联合化疗治疗子宫肉瘤的基因组特征。此外，每位患者的基因突变数量都很大。
