小狗阅读会员会员
有解析的医学SCI阅读工具

扫码登录小狗阅读

阅读SCI医学文献

Prevalence of somatic and germline mutations of Fumarate hydratase in uterine leiomyomas from young patients.

年轻患者子宫肌瘤富马酸水合酶体细胞和生殖系突变的患病率。

  • 影响因子:2.67
  • DOI:10.1111/his.14007
  • 作者列表:"Liu C","Dillon J","Beavis AL","Liu Y","Lombardo K","Fader AN","Hung CF","Wu TC","Vang R","Garcia JE","Xing D
  • 发表时间:2020-02-01
Abstract

AIMS:Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is caused by germline mutations in the Fumarate hydratase (FH) gene. In young women, the syndrome often presents with symptomatic uterine leiomyomas, leading to myomectomy or hysterectomy. In this study, we aimed to investigate the incidence and mutational profiles of FH-negative leiomyomas from young patients, thus allowing for early identification and triage of syndromic patients for surveillance. METHODS AND RESULTS:We evaluated 153 cases of uterine leiomyomas from women aged up to 30 years for loss of FH expression by tissue microarray (TMA)-based immunohistochemical staining. Mutational analysis of tumours with loss of FH was carried out by polymerase chain reaction (PCR) amplification of 10 exons within the FH gene and subsequent Sanger sequencing. The status of promoter methylation was assessed by bisulphite sequencing. Loss of FH protein expression was detected in seven (4.6%) of 153 tested uterine leiomyomas from young patients. All FH-negative leiomyomas displayed staghorn vasculature and fibrillary/neurophil-like cytoplasm. We found that six (86%) of seven FH-negative tumours detected by immunohistochemistry harboured FH mutations, 50% of which contained germline mutations. In particular, the germline mutational rate in FH gene was 2.0% (three of 153 cases). Bisulphite sequencing analysis failed to detect promoter methylation in any of the seven tumours. CONCLUSION:Our study showed a relatively high rate of FH germline mutation in FH-negative uterine leiomyomas from patients aged up to 30 years. While genetic mutations confer protein expression loss, epigenetic regulation of the FH gene appears to be unrelated to this phenotype.

摘要

目的: 遗传性平滑肌瘤病和肾细胞癌 (HLRCC) 综合征是由富马酸水合酶 (FH) 基因的生殖系突变引起的。在年轻女性中,该综合征通常表现为症状性子宫肌瘤,导致子宫肌瘤切除术或子宫切除术。在这项研究中,我们旨在调查年轻患者中 FH 阴性平滑肌瘤的发生率和突变特征,从而对综合征患者进行早期识别和分诊以进行监测。 方法和结果: 我们通过基于组织芯片 (TMA) 的免疫组织化学染色评价了 153 例 30 岁以下女性子宫平滑肌瘤 FH 表达缺失。通过聚合酶链反应 (PCR) 扩增 FH 基因内的 10 个外显子并随后进行 Sanger 测序,对 FH 缺失的肿瘤进行突变分析。通过亚硫酸氢盐测序评估启动子甲基化状态。在来自年轻患者的 4.6% 例受检子宫肌瘤中,7 例 (153) 检测到 FH 蛋白表达缺失。所有 FH 阴性的平滑肌瘤均显示鹿角状脉管系统和纤维/神经样细胞质。我们发现免疫组化检测到的 7 例 FH 阴性肿瘤中有 6 例 (86%) 存在 FH 突变,其中 50% 包含生殖系突变。FH 基因的种系突变率为 2.0% (153 例中有 3 例)。亚硫酸氢盐测序分析未能在 7 个肿瘤中的任何一个中检测到启动子甲基化。 结论: 我们的研究显示 30 岁以下患者 FH 阴性子宫肌瘤中 FH 生殖系突变率相对较高。虽然基因突变导致蛋白表达缺失,但 FH 基因的表观遗传调控似乎与该表型无关。

下载该文献
小狗阅读

帮助医生、学生、科研工作者解决SCI文献找不到、看不懂、阅读效率低的问题。提供领域精准的SCI文献,通过多角度解析提高文献阅读效率,从而使用户获得有价值研究思路。

相关文献
影响因子:1.69
发表时间:2020-01-01
DOI:10.1016/j.jmig.2019.03.015
作者列表:["Oxley SG","Mallick R","Odejinmi F"]

METHODS:STUDY OBJECTIVE:To evaluate the differences in perioperative outcomes and immediate complication rates between laparoscopic myomectomy for submucous myomas and laparoscopic myomectomy for myomas in other locations. DESIGN:Retrospective cohort study. SETTING:University-affiliated hospital in London. PATIENTS:A total of 350 patients with symptomatic uterine myomas underwent laparoscopic myomectomy. Thirty-three of these were performed for submucous myomas (group 1), and 317 were for myomas in other uterine locations (group 2). INTERVENTIONS:Analysis of prospectively collected data on patient demographics, myoma characteristics, perioperative outcomes, and immediate complications. MEASUREMENTS AND MAIN RESULTS:Patient demographics, including age, body mass index, and parity, were similar in the 2 groups. No significant differences in myoma characteristics were seen between groups 1 and 2, including the mean dimension of largest myoma (7.1 vs 7.8 cm, respectively; p = .35), mean number of myomas removed (3.8 vs 4.1; p = .665), and mean mass of myomas removed (142.0 g vs 227.3 g; p = .186). There were also no significant between-group differences in any perioperative outcomes, including mean blood loss (226.8 mL vs 266.4 mL; p = .373), duration of surgery (103 minutes vs 113 minutes; p = .264), and duration of hospital stay (1.4 days vs 1.7 days; p = .057). No complications arose from laparoscopic resection of submucous myomas. CONCLUSION:Laparoscopic myomectomy for submucous myomas has similar perioperative outcomes and immediate complications as laparoscopic myomectomy for other myomas and can be considered for large or type 2 submucous myomas.

翻译标题与摘要 下载文献
影响因子:2.21
发表时间:2020-01-01
DOI:10.1111/aogs.13713
作者列表:["de Milliano I","Huirne JAF","Thurkow AL","Radder C","Bongers MY","van Vliet H","van de Lande J","van de Ven PM","Hehenkamp WJK"]

METHODS:INTRODUCTION:Laparoscopic myomectomy can be difficult when fibroids are large and numerous. This may result in extensive intraoperative bleeding and the need for a conversion to a laparotomy. Medical pretreatment prior to surgery might reduce these risks by decreasing fibroid size and vascularization of the fibroid. We compared pretreatment with ulipristal acetate (UPA) vs gonadotropin-releasing hormone agonists (GnRHa) prior to laparoscopic myomectomy on several intra- and postoperative outcomes. MATERIAL AND METHODS:We performed a non-inferiority double-blind randomized controlled trial in nine hospitals in the Netherlands. Women were randomized between daily oral UPA for 12 weeks and single placebo injection or single intramuscular injection with leuprolide acetate and daily placebo tablets for 12 weeks. The primary outcome was intraoperative blood loss. Secondary outcomes were reduction of fibroid volume, suturing time, total surgery time and surgical ease. RESULTS:Thirty women received UPA and 25 women leuprolide acetate. Non-inferiority of UPA regarding intraoperative blood loss was not demonstrated. When pretreated with UPA, median intraoperative blood loss was statistically significantly higher (525 mL [348-1025] vs 280 mL[100-500]; P = 0.011) and suturing time of the first fibroid was statistically significantly longer (40 minutes [28-48] vs 22 minutes [14-33]; P = 0.003) compared with GnRHa. Pretreatment with UPA showed smaller reduction in fibroid volume preoperatively compared with GnRHa (-7.2% [-35.5 to 54.1] vs -38.4% [-71.5 to -19.3]; P = 0.001). Laparoscopic myomectomies in women pretreated with UPA were subjectively judged more difficult than in women pretreated with GnRHa. CONCLUSIONS:Non-inferiority of UPA in terms of intraoperative blood loss could not be established, possibly due to the preliminary termination of the study. Pretreatment with GnRHa was more favorable than UPA in terms of fibroid volume reduction, intraoperative blood loss, hemoglobin drop directly postoperatively, suturing time of the first fibroid and several subjective surgical ease parameters.

影响因子:2.67
发表时间:2020-02-01
来源期刊:Histopathology
DOI:10.1111/his.14007
作者列表:["Liu C","Dillon J","Beavis AL","Liu Y","Lombardo K","Fader AN","Hung CF","Wu TC","Vang R","Garcia JE","Xing D"]

METHODS:AIMS:Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is caused by germline mutations in the Fumarate hydratase (FH) gene. In young women, the syndrome often presents with symptomatic uterine leiomyomas, leading to myomectomy or hysterectomy. In this study, we aimed to investigate the incidence and mutational profiles of FH-negative leiomyomas from young patients, thus allowing for early identification and triage of syndromic patients for surveillance. METHODS AND RESULTS:We evaluated 153 cases of uterine leiomyomas from women aged up to 30 years for loss of FH expression by tissue microarray (TMA)-based immunohistochemical staining. Mutational analysis of tumours with loss of FH was carried out by polymerase chain reaction (PCR) amplification of 10 exons within the FH gene and subsequent Sanger sequencing. The status of promoter methylation was assessed by bisulphite sequencing. Loss of FH protein expression was detected in seven (4.6%) of 153 tested uterine leiomyomas from young patients. All FH-negative leiomyomas displayed staghorn vasculature and fibrillary/neurophil-like cytoplasm. We found that six (86%) of seven FH-negative tumours detected by immunohistochemistry harboured FH mutations, 50% of which contained germline mutations. In particular, the germline mutational rate in FH gene was 2.0% (three of 153 cases). Bisulphite sequencing analysis failed to detect promoter methylation in any of the seven tumours. CONCLUSION:Our study showed a relatively high rate of FH germline mutation in FH-negative uterine leiomyomas from patients aged up to 30 years. While genetic mutations confer protein expression loss, epigenetic regulation of the FH gene appears to be unrelated to this phenotype.

方向

复制标题
发送后即可在该邮箱或我的下载查看该文献
发送
该文献默认存储到我的下载

科研福利

报名咨询

建议反馈
问题标题:
联系方式:
电子邮件:
您的需求: