Kazanci Ferah, Çelik Zerrin Yılmaz, Polat Mert, Karademir Ferhat, Erdem Ozlem, Şahin Feride İffet, Onan Mehmet Anil
Gazi University, Faculty of Medicine, Department of Gynaecologic Oncology - Ankara, Turkey.
Baskent University, Faculty of Medicine, Department of Medical Genetics - Ankara, Turkey.
Rev Assoc Med Bras (1992). 2024 Sep 30;70(10):e20240534. doi: 10.1590/1806-9282.20240534. eCollection 2024.
The objective of this study was to analyze the genetic alterations of tumors within the scope of the homologous recombination deficiency gene panel in patients diagnosed with synchronous endometrial ovarian cancer who have been followed for over 5 years using next-generation sequencing.
DNA was isolated from the patient's formalin-fixed, paraffin-embedded tissue blocks. Next-generation sequencing was performed using the Illumina capture-based sequencing method. Samples were sequenced using the Sophia HR Solution DNA Kit.
Seven patients were included in this study. The ratios of likely pathogenic (LP)/pathogenic (P) somatic mutations in ATM (serine/threonine kinase or Ataxia-telangiectasia mutated gene), BRCA2 (breast cancer type 2 susceptibility gene), BARD1 (BRCA1 associated RING domain 1), TP53 (tumor protein p53), BIRP1 (BRCA1-interacting helicase 1 gene), PALB2 (partner and localizer of BRCA2), and CHECK2 were 21 (48.8%), 8 (18.6%), 5 (11.6%), 3 (6.9%), 2 (4.6%), 2 (4.6%), and 2 (4.6%), respectively, in endometrium, and the ratios of somatic mutations in ATM, BRCA2, TP53, BARD1, RAD54L (DNA repair/recombination protein like), BIRP1, and RAD51D (RAD51 recombinase paralog D) were 24 (60%), 6 (15%), 5 (12.5%), 2 (5%), 2 (5%), 1 (2.5%), and 1 (2.5%), respectively, in ovary. In endometrioid-synchronous endometrial ovarian cancer cases, P/LP mutations were observed in ATM and CHECK2 genes in endometrium and ATM, BRCA2, and TP53 genes in ovary. In two non-endometrioid-synchronous endometrial ovarian cancer cases, CHEK2 (checkpoint kinase 2) mutations were observed in endometrium and ATM and TP53 mutations in ovary, whereas in one case, P/LP mutations in ATM and TP53 genes were common in both tissues.
Pathogenic variations confirming the diagnosis of synchronous endometrial ovarian cancer with genetic alterations were identified in all but one case. ATM gene mutation emerged as the most common alteration and has a potential association with a favorable prognosis.
本研究的目的是使用下一代测序技术分析诊断为同步性子宫内膜癌和卵巢癌且随访超过5年的患者中同源重组缺陷基因panel范围内肿瘤的基因改变。
从患者的福尔马林固定、石蜡包埋组织块中提取DNA。使用基于Illumina捕获的测序方法进行下一代测序。样本使用Sophia HR Solution DNA试剂盒进行测序。
本研究纳入7例患者。子宫内膜中，ATM（丝氨酸/苏氨酸激酶或共济失调毛细血管扩张突变基因）、BRCA2（乳腺癌2型易感基因）、BARD1（BRCA1相关环结构域1）、TP53（肿瘤蛋白p53）、BIRP1（BRCA1相互作用解旋酶1基因）、PALB2（BRCA2的伴侣和定位蛋白）和CHECK2的可能致病（LP）/致病（P）体细胞突变率分别为21（48.8%）、8（18.6%）、5（11.6%）、3（6.9%）、2（4.6%）、2（4.6%）和2（4.6%），卵巢中ATM、BRCA2、TP53、BARD1、RAD54L（类DNA修复/重组蛋白）、BIRP1和RAD51D（RAD51重组酶旁系同源物D）的体细胞突变率分别为24（60%）、6（15%）、5（12.5%）、2（5%）、2（5%）、1（2.5%）和1（2.5%）。在子宫内膜样同步性子宫内膜癌和卵巢癌病例中，子宫内膜中ATM和CHECK2基因以及卵巢中ATM、BRCA2和TP53基因存在P/LP突变。在2例非子宫内膜样同步性子宫内膜癌和卵巢癌病例中，子宫内膜中观察到CHEK2（检查点激酶2）突变，卵巢中观察到ATM和TP53突变，而在1例病例中，ATM和TP53基因的P/LP突变在两种组织中均常见。
除1例病例外，所有病例均鉴定出证实同步性子宫内膜癌和卵巢癌诊断且伴有基因改变的致病变异。ATM基因突变是最常见的改变，且可能与良好预后相关。
