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RRSO样本中p53特征的变异及浆液性输卵管原位癌的克隆性

variants in p53 signatures and the clonality of STICs in RRSO samples.

作者信息

Akahane Tomoko, Masuda Kenta, Hirasawa Akira, Kobayashi Yusuke, Ueki Arisa, Kawaida Miho, Misu Kumiko, Nakamura Kohei, Nagai Shimpei, Chiyoda Tatsuyuki, Yamagami Wataru, Hayashi Shigenori, Kataoka Fumio, Banno Kouji, Sugano Kokichi, Okita Hajime, Kosaki Kenjiro, Nishihara Hiroshi, Aoki Daisuke

机构信息

Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.

Genomics Unit, Keio Cancer Center, Keio University School of Medicine, Tokyo, Japan.

出版信息

J Gynecol Oncol. 2022 Jul;33(4):e50. doi: 10.3802/jgo.2022.33.e50. Epub 2022 Mar 21.

Abstract

OBJECTIVE

Precursor lesions may be identified in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in patients with pathogenic variants of . Serous tubal intraepithelial carcinoma (STIC) is considered a precursor of high-grade serous carcinoma, whereas the significance of the p53 signature remains unclear. In this study, we investigated the relationship between the p53 signature and the risk of ovarian cancer.

METHODS

We analyzed the clinicopathological findings and conducted DNA sequencing for variants of p53 signatures and STIC lesions isolated using laser capture microdissection in 13 patients with pathogenic variants of who underwent RRSO and 17 control patients with the benign gynecologic disease.

RESULTS

pathogenic variants were detected significantly higher in RRSO group than control (p<0.001). No difference in the frequency of p53 signatures were observed between groups (53.8% vs 29.4%; p=0.17). sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 mutations causing different p53 staining for STICs and another mutation shared between STIC and occult cancer.

CONCLUSION

The sequence analysis for revealed 2 types of p53 signatures, one with a risk of progression to STIC and ovarian cancer with pathological variants in and the other with a low risk of progression without pathological variants in as seen in control.

摘要

目的

在携带某种致病基因变异的患者进行降低风险的输卵管卵巢切除术(RRSO)后,可在输卵管组织中识别出前驱病变。浆液性输卵管上皮内癌(STIC)被认为是高级别浆液性癌的前驱病变,而p53特征的意义仍不明确。在本研究中,我们调查了p53特征与卵巢癌风险之间的关系。

方法

我们分析了13例携带某种致病基因变异并接受RRSO的患者以及17例患有良性妇科疾病的对照患者的临床病理结果,并对使用激光捕获显微切割分离出的p53特征变异和STIC病变进行了DNA测序。

结果

RRSO组中某种致病基因变异的检测率显著高于对照组(p<0.001)。两组之间p53特征的频率没有差异(53.8%对29.4%;p=0.17)。对一名患有STIC和隐匿性癌症的患者进行的某种基因测序和下一代测序分析显示,有2个某种基因突变导致STIC出现不同的p53染色,另外还有1个突变在STIC和隐匿性癌症之间共享。

结论

某种基因的序列分析揭示了2种p53特征类型,一种具有进展为STIC和卵巢癌的风险,伴有某种基因的病理变异,另一种进展风险较低,如对照组所见,不伴有某种基因的病理变异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/701e/9250861/4fa5fe25555f/jgo-33-e50-g001.jpg

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