妇科恶性肿瘤患者ERBB2/HER2基因扩增的分子景观；临床意义和未来方向
Molecular landscape of ERBB2/HER2 gene amplification among patients with gynecologic malignancies; clinical implications and future directions
影响因子:4.10000
分区:医学2区 Top / 妇产科学1区 肿瘤学2区
发表日期:2024 Jan
作者:
Dimitrios Nasioudis, Stefan Gysler, Nawar Latif, Lory Cory, Robert L Giuntoli, Sarah H Kim, Fiona Simpkins, Lainie Martin, Emily M Ko
摘要
研究了妇科恶性肿瘤患者中ERBB2/HER2基因扩增的流行。选择了有关存在拷贝基因改变的可用数据的患者以进行进一步分析。评估了通过肿瘤部位和组织学分层后ERBB2扩增的发生率。由CBIOPORTAL提供的OncoKB数据库的数据用于确定致病性基因组改变的存在。确定了符合纳入标准的6961例患者：49.1％患有卵巢癌，45.2％患有子宫内膜癌和5.7％患有宫颈癌。 ERBB2扩增的总体发生率为3.8％。在粘液卵巢（14.4％），子宫浆液（13.2％），子宫透明细胞（9.4％）和子宫癌（7.9％）的患者中，观察到ERBB2扩增的发病率最高。在TP53野生型子宫内膜类子宫内膜癌（0.4％）的患者中，ERBB2扩增很少见。在ERBB2扩增的肿瘤患者中，观察到PI3K途径基因突变的高发病率。ERBB2扩增在子宫浆液性癌癌和粘膜卵巢癌中经常遇到。此外，在子宫透明细胞癌和子宫癌的患者中还观察到高发病率。对于子宫内膜类子宫内膜癌的患者，ERBB2扩增的发生率很低，尤其是在没有TP53突变的情况下。
Abstract
Investigate the prevalence of ERBB2/HER2 gene amplification among patients with gynecologic malignancies.The American Association of Cancer Research (AACR) Genomics Evidence of Neoplasia Information Exchange (GENIE) (version 13.1) database was accessed and patients with endometrial, ovarian, and cervical cancer were identified. Patients with available data on the presence of copy-number gene alterations were selected for further analysis. Incidence of ERBB2 amplification following stratification by tumor site and histology was evaluated. Data from the OncoKB database, as provided by cBioPortal, was utilized to determine presence of pathogenic genomic alterations.A total of 6961 patients who met the inclusion criteria were identified: 49.1% with ovarian cancer, 45.2% with endometrial cancer and 5.7% with cervical cancer respectively. Overall incidence of ERBB2 amplification was 3.8%. Highest incidence of ERBB2 amplification was observed among patients with mucinous ovarian (14.4%), uterine serous (13.2%), uterine clear cell (9.4%), and uterine carcinosarcoma (7.9%). ERBB2 amplification was rare among patients with TP53 wild-type endometrioid endometrial cancer (0.4%). High incidence of mutations in genes of the PI3K pathway was observed among patients with ERBB2 amplified tumors.ERBB2 amplification is frequently encountered among patients with uterine serous carcinoma, and mucinous ovarian carcinoma. In addition, a high incidence was also observed among those with uterine clear cell carcinoma, and uterine carcinosarcoma. For patients with endometrioid endometrial carcinoma, incidence of ERBB2 amplification is low, especially in the absence of TP53 mutations.