Identifying occult maternal malignancies from 1.93 million pregnant women undergoing noninvasive prenatal screening tests

被引：39

作者：

Ji, Xing ^{[1
,2
]}

Li, Jia ^{[3
]}

Huang, Yonghua ^{[4
]}

Sung, Pi-Lin ^{[5
,6
]}

Yuan, Yuying ^{[3
]}

Liu, Qiang ^{[3
]}

Chen, Yan ^{[3
]}

Ju, Jia ^{[3
]}

Zhou, Yafeng ^{[3
]}

Huang, Shujia ^{[3
]}

Chen, Fang ^{[3
]}

Han, Yuan ^{[7
]}

Yuan, Wen ^{[7
]}

Fan, Cheng ^{[3
]}

Zhao, Qiang ^{[4
]}

Wu, Haitao ^{[8
]}

Feng, Suihua ^{[4
]}

Liu, Weiqiang ^{[9
]}

Li, Zhihua ^{[10
]}

Chen, Jingsi ^{[10
]}

Chen, Min ^{[10
]}

Yao, Hong ^{[11
]}

Zeng, Li ^{[12
]}

Ma, Tao ^{[13
]}

Fan, Shushu ^{[14
]}

Zhang, Jinman ^{[15
,16
]}

Yuen, Ka Yiu ^{[17
]}

Cheng, So Hin ^{[17
]}

Chik, Irene Wing Shan ^{[17
]}

Liu, Nien-Tzu ^{[17
]}

Zhu, Jianyu ^{[3
]}

Lin, Siyuan ^{[17
]}

Cao, Jeremy ^{[17
]}

Tong, Steve ^{[17
]}

Shan, Zhiyuan ^{[18
]}

Li, Wenyan ^{[3
]}

Hekmat, Mohammad Reza ^{[19
]}

Garshasbi, Masoud ^{[19
,20
]}

Suela, Javier ^{[21
]}

Torres, Yaima ^{[21
]}

Cigudosa, Juan C. ^{[21
]}

Perez Ruiz, F. J. ^{[22
]}

Rodriguez, Laura ^{[23
]}

Garcia, Monica ^{[23
]}

Bernik, Janez ^{[24
]}

Traven, Eva ^{[24
]}

Res, Ursula ^{[25
]}

Tul, Natasa ^{[26
]}

Tseng, Ching-Fong ^{[27
]}

Zhao, Depeng ^{[28
]}

机构：

[1] Shanghai Jiao Tong Univ, Xin Hua Hosp, Sch Med, Ctr Clin Genet, Shanghai, Peoples R China

[2] Shanghai Inst Pediat Res, Dept Genet, Shanghai, Peoples R China

[3] BGI Shenzhen, BGI Genom, Shenzhen, Guangdong, Peoples R China

[4] Sun Yat Sen Univ, Affiliated Jiangmen Hosp, Jiangmen Cent Hosp, Dept Obstet & Gynecol, Jiangmen, Guangdong, Peoples R China

[5] Taipei Vet Gen Hosp, Dept Obstet & Gynecol, Taipei, Taiwan

[6] Natl Yang Ming Univ, Sch Med, Dept Obstet & Gynecol, Taipei, Taiwan

[7] BGI Shenzhen, BGI Wuhan, Wuhan, Guangdong, Peoples R China

[8] Sun Yat Sen Univ, Affiliated Jiangmen Hosp, Jiangmen Cent Hosp, Reprod Med Ctr, Jiangmen, Guangdong, Peoples R China

[9] Guangzhou Med Univ, Affiliated Hosp 3, Key Lab Major Obstetr Dis Guangdong, Key Lab Reprod & Genet,Guangdong Higher Educ Inst, Guangzhou, Guangdong, Peoples R China

[10] Guangzhou Med Univ, Affiliated Hosp 3, Dept Prenatal Diag & Fetal Med, Guangzhou, Guangdong, Peoples R China

[11] Southwest Hosp, Prenatal Diag Ctr, Chongqing, Peoples R China

[12] Bazhong Cent Hosp, Dept Obstet & Gynecol, Bazhong, Sichuan, Peoples R China

[13] Sichuan Prov Peoples Hosp, Dept Obstet & Gynecol, Chengdu, Sichuan, Peoples R China

[14] Yue Bei Peoples Hosp, Genet Diag Ctr & Reprod Ctr, Shaoguan, Guangdong, Peoples R China

[15] Kunming Univ Sci & Technol, Fac Environm Sci & Engn, Kunming, Yunnan, Peoples R China

[16] First Peoples Hosp Yunnan, Genet Diag Ctr, Kunming, Yunnan, Peoples R China

[17] BGI Hlth HK, Hong Kong, Peoples R China

[18] BGI Europe AS, Copenhagen, Denmark

[19] DeNA Lab, Dept Med Genet, Tehran, Iran

[20] Tarbiat Modares Univ, Fac Med Sci, Dept Med Genet, Tehran, Iran

[21] NIMGenetics, Madrid, Spain

[22] Hosp Gen San Jorge, Serv Ginecol & Obstetricia, Huesca, Spain

[23] Hosp HM, Lab Genet Mol AbaCid, Madrid, Spain

[24] GenePlanet Ltd, Ljubljana, Slovenia

[25] Dravlje Hlth Ctr IVF, Ljubljana, Slovenia

[26] Univ Med Ctr, Dept Perinatol, Div Obstet & Gynecol, Ljubljana, Slovenia

[27] Gene Hlth Co Ltd, Taipei, Taiwan

[28] Tongji Univ, Shanghai Matern & Infant Hosp 1, Dept Prenatal Diag & Fetal Med, Sch Med, Shanghai, Peoples R China

[29] Yangzhou Univ, Huaian Matern & Child Hlth Care Hosp Jiangsu Prov, Lab Clin Genet, Huaian, Jiangsu, Peoples R China

[30] Shanghai Pu Nan Hosp, Dept Pathol, Shanghai, Peoples R China

[31] James D Watson Inst Genome Sci, Hangzhou, Zhejiang, Peoples R China

[32] Univ Copenhagen, Dept Biol, Copenhagen, Denmark

[33] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, Singapore, Singapore

[34] South China Univ Technol, Sch Med, Guangzhou, Guangdong, Peoples R China

[35] BGI Shenzhen, BGI Guangzhou Med Lab, Guangzhou, Guangdong, Peoples R China

来源：

GENETICS IN MEDICINE | 2019年 / 21卷 / 10期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

Noninvasive prenatal screening test; Maternal malignancy; Multiple chromosomal aneuploidies; Cancer detection; Plasma tumor marker; INCIDENTAL DETECTION; CLINICAL UTILITY; CANCER; EXPERIENCE; TRISOMIES;

D O I：

10.1038/s41436-019-0510-5

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Purpose: Multiple chromosomal aneuploidies may be associated with maternal malignancies and can cause failure of noninvasive prenatal screening (NIPS) tests. However, multiple chromosomal aneuploidies show poor specificity and selectivity for diagnosing maternal malignancies. Methods: This multicenter retrospective analysis evaluated 639 pregnant women who tested positive for multiple chromosomal aneuploidies on initial NIPS test between January 2016 and December 2017. Women were assessed using genome profiling of copy-number variations, which was translated to cancer risk using a novel bioinformatics algorithm called the cancer detection pipeline (CDP). Sensitivity, specificity, and positive predictive value (PPV) of diagnosing maternal malignancies were compared for multiple chromosomal aneuploidies, the CDP model, and the combination of CDP and plasma tumor markers. Results: Of the 639 subjects, 41 maternal malignant cancer cases were diagnosed. Multiple chromosomal aneuploidies predicted maternal malignancies with a PPV of 7.6%. Application of the CDP algorithm to women with multiple chromosomal aneuploidies allowed 34 of the 41 (83%) cancer cases to be identified, while excluding 422 of 501 (84.2%) of the false positive cases. Combining the CDP with plasma tumor marker testing gave PPV of 75.0%. Conclusion: The CDP algorithm can diagnose occult maternal malignancies with a reasonable PPV in multiple chromosomal aneuploidies-positive pregnant women in NIPS tests. This performance can be further improved by incorporating findings for plasma tumor markers.

引用

页码：2293 / 2302

页数：10

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