TP53 variants in p53 signatures and the clonality of STICs in RRSO samples.
TP53 variants in p53 signatures and the clonality of STICs in RRSO samples.
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DOI：
10.3802/jgo.2022.33.e50
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发表时间：
2022-07
影响因子：
3.9
通讯作者：
Aoki, Daisuke
中科院分区：
文献类型：
--
作者：
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
关键词：
BRCA1/2致病变异型患者行降低风险输卵管卵巢切除术(RRSO)后，可在输卵管组织中发现前驱病变。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，但P53信号的意义尚不清楚。在这项研究中，我们调查了P53签名与卵巢癌风险的关系。我们分析了13例BRCA1/2致病变异体患者行RRSO手术后的临床病理结果，并对其中17例妇科良性疾病患者进行了p53信号TP53变异体和激光捕获显微切割分离的STIC病变的DNA测序。RRSO组检出的TP53致病变异体显著高于对照组(P<；0.001)。两组间P53签名频率差异无统计学意义(53.8%vs29.4%；p=0.17)。对1例STIC和隐匿性癌患者进行的TP53测序和下一代测序分析发现，2个TP53突变导致STIC的p53染色不同，另一个TP53突变在STIC和隐匿性癌之间共享。对TP53的序列分析揭示了两种类型的p53信号，一种是有进展风险的STIC和卵巢癌，其中有TP53的病理变异，另一种是与对照组一样，在TP53中没有病理变异的进展风险很低。我们对BRCA1/2致病变异型患者的p53信号中的TP53变异体进行了DNA测序，这些患者接受了降低风险的输卵管卵巢切除术(RRSO)，并与良性妇科疾病患者进行了对照。RRSO组TP53致病变异体的检出率明显高于RRSO组。根据BRCA状态的不同，P53签名的特征可能不同。
Precursor lesions may be identified in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in patients with pathogenic variants of BRCA1/2. 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. We analyzed the clinicopathological findings and conducted DNA sequencing for TP53 variants of p53 signatures and STIC lesions isolated using laser capture microdissection in 13 patients with pathogenic variants of BRCA1/2 who underwent RRSO and 17 control patients with the benign gynecologic disease. TP53 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). TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer. The sequence analysis for TP53 revealed 2 types of p53 signatures, one with a risk of progression to STIC and ovarian cancer with pathological variants in TP53 and the other with a low risk of progression without pathological variants in TP53 as seen in control. We conducted a DNA sequencing for TP53 variants in p53 signatures from patients with pathogenic variants of BRCA1/2 who underwent risk-reducing salpingo-oophorectomy (RRSO) and control patients with the benign gynecologic disease. TP53 pathogenic variants were detected significantly higher in RRSO group. The characteristics of p53 signatures might be different depending on BRCA status.
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影响因子：
7.3
作者：
Ahmed, Ashour Ahmed;Etemadmoghadam, Dariush;Temple, Jillian;Lynch, Andy G.;Riad, Mohamed;Sharma, Raghwa;Stewart, Colin;Fereday, Sian;Caldas, Carlos;DeFazio, Anna;Bowtell, David;Brenton, James D.
通讯作者：
Brenton, James D.
影响因子：
16.6
作者：
Labidi-Galy SI;Papp E;Hallberg D;Niknafs N;Adleff V;Noe M;Bhattacharya R;Novak M;Jones S;Phallen J;Hruban CA;Hirsch MS;Lin DI;Schwartz L;Maire CL;Tille JC;Bowden M;Ayhan A;Wood LD;Scharpf RB;Kurman R;Wang TL;Shih IM;Karchin R;Drapkin R;Velculescu VE
通讯作者：
Velculescu VE
影响因子：
120.7
作者：
Kuchenbaecker, Karoline B.;Hopper, John L.;Antoniou, Antonis C.
通讯作者：
Antoniou, Antonis C.
DOI：
10.1097/01.pgp.0000101082.35393.84
发表时间：
2004-01-01
影响因子：
2.4
作者：
Carcangiu, ML;Radice, P;Pasini, B
通讯作者：
Pasini, B
影响因子：
4.7
作者：
Leeper, K;Garcia, R;Paley, P
通讯作者：
Paley, P