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首页> 外文期刊>Gynecologic Oncology: An International Journal >LINE-1 retrotransposon-mediated DNA transductions in endometriosis associated ovarian cancers
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LINE-1 retrotransposon-mediated DNA transductions in endometriosis associated ovarian cancers

机译：第1线-1反向转移介导的子宫内膜异位症相关卵巢癌的DNA转导

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Abstract Objective Endometrioid (ENOC) and clear cell ovarian carcinoma (CCOC) share a common precursor lesion, endometriosis, hence the designation endometriosis associated ovarian cancers (EAOC). Long interspersed nuclear element 1 (LINE-1 or L1), is a family of mobile genetic elements activated in many cancers capable of moving neighboring DNA through 32 transductions. Here we investigated the involvement of specific L1-mediated transductions in EAOCs. Methods Through whole genome sequencing, we identified active L1-mediated transductions originating within the TTC28 gene in 34% (10/29) of ENOC and 31% (11/35) of CCOC cases. We used PCR and capillary sequencing to assess the presence of specific TTC28 -L1 transductions in formalin-fixed paraffin-embedded (FFPE) blocks from six different anatomical sites (five tumors and one normal control) for four ENOC and three CCOC cases, and compared the results to the presence of single nucleotide variations (SNVs)/frame shift (fs) mutations detected using multiplex PCR and next generation sequencing. Results TTC28 -L1 mediated transductions were identified in at least three tumor samplings in all cases, and were present in all five tumor samplings in 5/7 (71%) cases. In these cases, KRAS , PIK3CA , CTNNB1 , ARID1A , and PTEN mutations were found across all tumor sites while other selected SNV/fs mutations of unknown significance were present at varying allelic frequencies. Conclusion The TTC28- L1 transductions along with classical driver mutations were near ubiquitous across the tumors, suggesting that L1 activation likely occurred early in the development of EAOCs. TTC28- L1 transductions could potentially be used to determine clonal relationships and to track ovarian cancer progression. Highlights " An active LINE-1 retrotransposon from TTC28 gene is present in 32% of EAOCs. " TTC28 LINE-1 events are near ubiquitous across multiple EAOC tumor samplings. " TTC28 LINE-1 is likely activated early during EAOC development. " TTC28 LINE-1 may be used to track EAOC development.
机译：摘要目的子宫内疗法（ENOC）和透明细胞卵巢癌（CCOC）分享常见的前体病变，子宫内膜异位症，因此指定子宫内膜异位症相关卵巢癌（EAC）。长时间的核元素1（线-1或L1）是一种在许多癌症中激活的移动遗传元素系列，其能够通过32个转换移动相邻的DNA。在这里，我们调查了特定L1介导的转体在EAOC中的参与。方法通过全基因组测序，我们鉴定了源于CCOC病例的34％（10/29）的TTC28基因内的活性L1介导的转导。我们使用PCR和毛细管测序来评估来自六种不同的解剖部位（五种肿瘤和一个正常对照）的福尔马林固定的石蜡包埋（FFPE）嵌段的特异性TTC28 -L1转导的存在，并进行比较使用多重PCR和下一代测序检测到检测到单核苷酸变化（SNV）/帧移位（FS）突变的存在的结果。结果在所有情况下至少三种肿瘤采样中鉴定了TTC28 -L1介导的转导，并存在于5/7（71％）病例的所有五种肿瘤中。在这些情况下，在所有肿瘤位点发现KRA，PIK3CA，CTNNB1，ARID1A和PTEN突变，而其他选定的SNV / FS突变在不同的等位基因频率下存在未知意义。结论TTC28-L1转导随着经典的驾驶员突变在整个肿瘤上普遍存在，表明L1激活可能会在EACS的发展早期发生。 TTC28-L1转导可能用于确定克隆关系并跟踪卵巢癌进展。突出显示“来自TTC28基因的活跃线-1 Retrotransposon存在于32％的eAoc中。”TTC28线路-1事件越野横跨多个EAC肿瘤采样。 “TTC28 Line-1可能会在EAOC开发期间早期激活。”TTC28行-1可用于跟踪EAC开发。

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