Affinity-purified DNA-based mutation profiles of endometriosis-related ovarian neoplasms in Japanese patients.
Affinity-purified DNA-based mutation profiles of endometriosis-related ovarian neoplasms in Japanese patients.
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DOI：
10.18632/oncotarget.24546
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发表时间：
2018-03-13
期刊：
影响因子：
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通讯作者：
Kyo S
中科院分区：
文献类型：
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作者：
Ishikawa M;Nakayama K;Nakamura K;Ono R;Sanuki K;Yamashita H;Ishibashi T;Minamoto T;Iida K;Razia S;Ishikawa N;Kyo S
子宫内膜异位症相关的卵巢肿瘤（ERON）最近引起了相当大的关注，然而，在ERON的ARID 1A和POLE突变的患病率和模式还没有详细研究。本研究的目的不仅是调查ERON的致癌作用，而且在这个队列中的几个基因突变的预后意义。我们使用了从肿瘤上皮细胞中纯化的DNA，从肿瘤上皮细胞中去除了成纤维细胞，使用了我们称为“液体显微切割”的特定方法。使用了来自22个卵巢癌（13个卵巢样癌和9个透明细胞癌）的组织样本。使用细胞分选系统分离肿瘤细胞，并从肿瘤上皮细胞纯化DNA。进行核苷酸测序以分析ARID 1A、p53、PTEN、POLE、PIK 3CA和KRAS的突变状态。在ERON中，ARID 1A、p53、POLE、PTEN、PIK 3CA和KRAS的体细胞突变频率分别为19/20（95.0%）、7/19（36.8%）、9/22（40.9%）、13/19（68.4%）、3/19（15.8%）和1/9（11.1%）。ARID 1A突变的频率明显高于以前报道的。Kaplan-Meier生存分析显示，在我们的日本队列中，所有基因（包括POLE）的突变与患者预后无关。我们的研究结果表明，在ERON的ARID 1A突变的频率可能高于以前报道的。此外，我们选择的用于DNA纯化的“液体显微切割”方法可以用于获得高质量的测序结果。研究结果表明，ARID 1A突变代表了ERON致癌的基础;其他随后的基因突变可能导致致癌的进展。
Endometriosis-related ovarian neoplasms (ERONs) have recently attracted considerable attention; however, the prevalence and patterns of ARID1A and POLE mutations in ERONs have not been studied in detail. The aim of this study was to investigate not only the carcinogenesis of ERONs, but also the prognostic significance of several gene mutations in this cohort. We used DNA purified from only tumor epithelial cells, from which fibroblasts were removed, using a specific method we called “liquid microdissection”. Tissue samples from 22 ovarian carcinomas (13 endometrioid, and nine clear cell) were used. Tumor cells were isolated using a cell sorting system and DNA was purified from tumor epithelial cells. Nucleotide sequencing was conducted to analyze the mutational status of ARID1A, p53, PTEN, POLE, PIK3CA, and KRAS. In ERONs, the frequencies of somatic mutations in ARID1A, p53, POLE, PTEN, PIK3CA, and KRAS were 19/20 (95.0%), 7/19 (36.8%), 9/22 (40.9%), 13/19 (68.4%), 3/19 (15.8%), and 1/9 (11.1%). The frequency of ARID1A mutations was significantly higher than that reported previously. Kaplan-Meier survival analysis revealed that mutations in all genes, including POLE, were not associated with patient prognosis in our Japanese cohort. Our results suggest that the frequency of ARID1A mutations in ERONs may be higher than that previously reported. In addition, the “liquid microdissection” method that we chose for DNA purification could be used to obtain high-quality sequencing results. The findings suggest that ARID1A mutations represent the basis of ERON carcinogenesis; other subsequent gene mutations may result in the progression of carcinogenesis.