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中国卵巢癌患者体细胞改变的综合分析。

A comprehensive analysis of somatic alterations in Chinese ovarian cancer patients.

机构信息

Department of Gynecologic Oncology, Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Science, Hangzhou, People's Republic of China.

Department of Gynecological Surgery, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, People's Republic of China.

出版信息

Sci Rep. 2021 Jan 11;11(1):387. doi: 10.1038/s41598-020-79694-0.


DOI:10.1038/s41598-020-79694-0
PMID:33432021
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7801677/
Abstract

Ovarian cancer is one of the most common cancers in women and is often diagnosed as advanced stage because of the subtle symptoms of early ovarian cancer. To identify the somatic alterations and new biomarkers for the diagnosis and targeted therapy of Chinese ovarian cancer patients, a total of 65 Chinese ovarian cancer patients were enrolled for detection of genomic alterations. The most commonly mutated genes in ovarian cancers were TP53 (86.15%, 56/65), NF1 (13.85%, 9/65), NOTCH3 (10.77%, 7/65), and TERT (10.77%, 7/65). Statistical analysis showed that TP53 and LRP1B mutations were associated with the age of patients, KRAS, TP53, and PTEN mutations were significantly associated with tumor differentiation, and MED12, LRP2, PIK3R2, CCNE1, and LRP1B mutations were significantly associated with high tumor mutational burden. The mutation frequencies of LRP2 and NTRK3 in metastatic ovarian cancers were higher than those in primary tumors, but the difference was not significant (P = 0.072, for both). Molecular characteristics of three patients responding to olapanib supported that BRCA mutation and HRD related mutations is the target of olaparib in platinum sensitive patients. In conclusion we identified the somatic alterations and suggested a group of potential biomarkers for Chinese ovarian cancer patients. Our study provided a basis for further exploration of diagnosis and molecular targeted therapy for Chinese ovarian cancer patients.

摘要

卵巢癌是女性最常见的癌症之一,由于早期卵巢癌症状不明显,通常在晚期才被诊断出来。为了确定中国卵巢癌患者的体细胞改变和新的生物标志物,用于诊断和靶向治疗,共招募了 65 名中国卵巢癌患者进行基因组改变的检测。在卵巢癌中最常突变的基因是 TP53(86.15%,56/65)、NF1(13.85%,9/65)、NOTCH3(10.77%,7/65)和 TERT(10.77%,7/65)。统计分析显示,TP53 和 LRP1B 的突变与患者的年龄有关,KRAS、TP53 和 PTEN 的突变与肿瘤分化显著相关,而 MED12、LRP2、PIK3R2、CCNE1 和 LRP1B 的突变与高肿瘤突变负担显著相关。转移性卵巢癌中 LRP2 和 NTRK3 的突变频率高于原发性肿瘤,但差异无统计学意义(P=0.072,均)。对 3 名对奥拉帕尼有反应的患者的分子特征分析表明,BRCA 突变和 HRD 相关突变是奥拉帕尼在铂类敏感患者中的作用靶点。总之,我们确定了中国卵巢癌患者的体细胞改变,并提出了一组潜在的生物标志物。我们的研究为进一步探索中国卵巢癌患者的诊断和分子靶向治疗提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65a/7801677/4b0f59aca7f5/41598_2020_79694_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65a/7801677/34c78e535a83/41598_2020_79694_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65a/7801677/38ee7878f7ae/41598_2020_79694_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65a/7801677/39ea1ac4f4f3/41598_2020_79694_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65a/7801677/4b0f59aca7f5/41598_2020_79694_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65a/7801677/34c78e535a83/41598_2020_79694_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65a/7801677/38ee7878f7ae/41598_2020_79694_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65a/7801677/39ea1ac4f4f3/41598_2020_79694_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65a/7801677/4b0f59aca7f5/41598_2020_79694_Fig4_HTML.jpg

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J Ovarian Res. 2024-2-20

[4]
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[5]
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[6]
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J Gynecol Oncol. 2023-11

[7]
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[8]
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本文引用的文献

[1]
Actionable co-alterations in breast tumors with pathogenic mutations in the homologous recombination DNA damage repair pathway.

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Oncol Lett. 2020-4

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Cancer Res. 2019-9-17

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Germline and somatic mutations of multi-gene panel in Chinese patients with epithelial ovarian cancer: a prospective cohort study.

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New Challenges in Tumor Mutation Heterogeneity in Advanced Ovarian Cancer by a Targeted Next-Generation Sequencing (NGS) Approach.

Cells. 2019-6-14

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