Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Headquarters of the Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
Clin Chim Acta. 2019 Jul;494:1-7. doi: 10.1016/j.cca.2019.03.003. Epub 2019 Mar 6.
The objective of this study was to assess the mutational profile in epithelial ovarian cancer using formalin-fixed, paraffin-embedded (FFPE) tumor specimens from a Taiwanese population by performing targeted sequencing of 9 cancer-associated genes.
Targeted sequencing was performed on 32 formalin-fixed, paraffin embedded (FFPE) tumor specimens, consisting of matched samples from 16 epithelial ovarian cancer patients. Genetic alterations in the 9 cancer-associated genes were detected using a deep sequencing (>1000×) approach.
ARID1A and PIK3CA were the most frequently mutated genes. Specifically, ARID1A mutations and PIK3CA mutations were detected in 77.8% and 66.7% of ovarian clear cell carcinoma patients, respectively. Mutations in other genes, including MLH1 (6.3%) and CREBBP (6.3%), were detected in the Taiwanese population. We also identified coexisting ARID1A-PIK3CA mutations (43.8%) and ARID1A-KRAS mutations (12.5%) in tumors. It should also be noted that we identified the presence of three coexisting mutations, the ARID1A-KRAS-PIK3CA mutations and the ARID1A-CREBBP-PIK3CA mutations.
In summary, we identified novel genetic alterations in patients with epithelial ovarian carcinoma (EOC) in a Taiwanese populations. Further studies are needed to elucidate the mechanism of chromatin remodeling to examine the role of the PI3K/AKT pathway, to determine the critical roles of these mechanisms in tumor development and the progression of ovarian malignancy and to investigate new targeted therapies. Overall, our findings were reliable and are worthy of further study.
本研究旨在通过对 9 个与癌症相关基因进行靶向测序，评估台湾人群福尔马林固定、石蜡包埋（FFPE）肿瘤标本中上皮性卵巢癌的突变谱。
对 32 例福尔马林固定、石蜡包埋（FFPE）肿瘤标本进行靶向测序，其中包括 16 例上皮性卵巢癌患者的配对样本。采用深度测序（>1000×）方法检测 9 个与癌症相关基因中的遗传改变。
ARID1A 和 PIK3CA 是最常突变的基因。具体而言，卵巢透明细胞癌患者中分别检测到 ARID1A 突变和 PIK3CA 突变的比例为 77.8%和 66.7%。在台湾人群中还检测到其他基因的突变，包括 MLH1（6.3%）和 CREBBP（6.3%）。我们还在肿瘤中发现了共存的 ARID1A-PIK3CA 突变（43.8%）和 ARID1A-KRAS 突变（12.5%）。此外，还发现了三种共存突变，即 ARID1A-KRAS-PIK3CA 突变和 ARID1A-CREBBP-PIK3CA 突变。
总之，我们在台湾人群中发现了上皮性卵巢癌（EOC）患者新的遗传改变。需要进一步研究阐明染色质重塑的机制，以研究 PI3K/AKT 通路的作用，确定这些机制在肿瘤发生和卵巢恶性肿瘤进展中的关键作用，并探索新的靶向治疗方法。总的来说，我们的研究结果是可靠的，值得进一步研究。
