Comparison of tumor-informed and tumor-naive sequencing assays for ctDNA detection in breast cancer

被引：24

作者：

Santonja, Angela ^{[1
,2
]}

Cooper, Wendy N. ^{[1
,2
]}

Eldridge, Matthew D. ^{[1
,2
]}

Edwards, Paul A. W. ^{[1
,2
,3
]}

Morris, James A. ^{[1
,2
]}

Edwards, Abigail R. ^{[1
]}

Zhao, Hui ^{[1
,2
]}

Heider, Katrin ^{[1
,2
]}

Couturier, Dominique-Laurent ^{[1
,2
,4
]}

Vijayaraghavan, Aadhitthya ^{[1
,2
]}

Mennea, Paulius ^{[1
,2
]}

Ditter, Emma-Jane ^{[1
,2
]}

Smith, Christopher G. ^{[1
,2
]}

Boursnell, Chris ^{[1
,2
]}

Garcia, Raquel Manzano ^{[1
,2
]}

Rueda, Oscar M. ^{[4
]}

Beddowes, Emma ^{[1
,2
]}

Biggs, Heather ^{[5
,6
]}

Sammut, Stephen-John ^{[1
,2
,5
]}

Rosenfeld, Nitzan ^{[1
,2
]}

Caldas, Carlos ^{[1
,2
,5
,6
]}

Abraham, Jean E. ^{[2
,5
,6
]}

Gale, Davina ^{[1
,2
]}

机构：

[1] Univ Cambridge, Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Cambridge, England

[2] Canc Res UK Cambridge Inst, Canc Res UK Cambridge Ctr, Li Ka Shing Ctr, Cambridge, England

[3] Univ Cambridge, Dept Pathol, Cambridge, England

[4] Univ Cambridge, MRC Biostat Unit, Cambridge, England

[5] Univ Cambridge, Dept Oncol, Cambridge, England

[6] Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Precis Breast Canc Inst, Cambridge, England

来源：

EMBO MOLECULAR MEDICINE | 2023年 / 15卷 / 06期

基金：

欧洲研究理事会; 英国惠康基金;

关键词：

circulating tumor DNA; liquid biopsy; hybrid capture; multiplex PCR; whole-genome sequencing; DNA ANALYSIS; PLASMA;

D O I：

10.15252/emmm.202216505

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Analysis of circulating tumor DNA (ctDNA) to monitor cancer dynamics and detect minimal residual disease has been an area of increasing interest. Multiple methods have been proposed but few studies have compared the performance of different approaches. Here, we compare detection of ctDNA in serial plasma samples from patients with breast cancer using different tumor-informed and tumor-naive assays designed to detect structural variants (SVs), single nucleotide variants (SNVs), and/or somatic copy-number aberrations, by multiplex PCR, hybrid capture, and different depths of whole-genome sequencing. Our results demonstrate that the ctDNA dynamics and allele fractions (AFs) were highly concordant when analyzing the same patient samples using different assays. Tumor-informed assays showed the highest sensitivity for detection of ctDNA at low concentrations. Hybrid capture sequencing targeting between 1,347 and 7,491 tumor-identified mutations at high depth was the most sensitive assay, detecting ctDNA down to an AF of 0.00024% (2.4 parts per million, ppm). Multiplex PCR targeting 21-47 tumor-identified SVs per patient detected ctDNA down to 0.00047% AF (4.7 ppm) and has potential as a clinical assay.

引用

页数：20

共 67 条

[1] Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution [J].

Abbosh, Christopher ;

Birkbak, Nicolai J. ;

Wilson, Gareth A. ;

Jamal-Hanjani, Mariam ;

Constantin, Tudor ;

Salari, Raheleh ;

Le Quesne, John ;

Moore, David A. ;

Veeriah, Selvaraju ;

Rosenthal, Rachel ;

Marafioti, Teresa ;

Kirkizlar, Eser ;

Watkins, Thomas B. K. ;

McGranahan, Nicholas ;

Ward, Sophia ;

Martinson, Luke ;

Riley, Joan ;

Fraioli, Francesco ;

Al Bakir, Maise ;

Gronroos, Eva ;

Zambrana, Francisco ;

Endozo, Raymondo ;

Bi, Wenya Linda ;

Fennessy, Fiona M. ;

Sponer, Nicole ;

Johnson, Diana ;

Laycock, Joanne ;

Shafi, Seema ;

Czyzewska-Khan, Justyna ;

Rowan, Andrew ;

Chambers, Tim ;

Matthews, Nik ;

Turajlic, Samra ;

Hiley, Crispin ;

Lee, Siow Ming ;

Forster, Martin D. ;

Ahmad, Tanya ;

Falzon, Mary ;

Borg, Elaine ;

Lawrence, David ;

Hayward, Martin ;

Kolvekar, Shyam ;

Panagiotopoulos, Nikolaos ;

Janes, Sam M. ;

Thakrar, Ricky ;

Ahmed, Asia ;

Blackhall, Fiona ;

Summers, Yvonne ;

Hafez, Dina ;

Naik, Ashwini .

NATURE, 2017, 545 (7655) :446-+

[2] Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors [J].

Adalsteinsson, Viktor A. ;

Ha, Gavin ;

Freeman, Samuel S. ;

Choudhury, Atish D. ;

Stover, Daniel G. ;

Parsons, Heather A. ;

Gydush, Gregory ;

Reed, Sarah C. ;

Rotem, Denisse ;

Rhoades, Justin ;

Loginov, Denis ;

Livitz, Dimitri ;

Rosebrock, Daniel ;

Leshchiner, Ignaty ;

Kim, Jaegil ;

Stewart, Chip ;

Rosenberg, Mara ;

Francis, Joshua M. ;

Zhang, Cheng-Zhong ;

Cohen, Ofir ;

Oh, Coyin ;

Ding, Huiming ;

Polak, Paz ;

Lloyd, Max ;

Mahmud, Sairah ;

Helvie, Karla ;

Merrill, Margaret S. ;

Santiago, Rebecca A. ;

O'Connor, Edward P. ;

Jeong, Seong H. ;

Leeson, Rachel ;

Barry, Rachel M. ;

Kramkowski, Joseph F. ;

Zhang, Zhenwei ;

Polacek, Laura ;

Lohr, Jens G. ;

Schleicher, Molly ;

Lipscomb, Emily ;

Saltzman, Andrea ;

Oliver, Nelly M. ;

Marini, Lori ;

Waks, Adrienne G. ;

Harshman, Lauren C. ;

Tolaney, Sara M. ;

Van Allen, Eliezer M. ;

Winer, Eric P. ;

Lin, Nancy U. ;

Nakabayashi, Mari ;

Taplin, Mary-Ellen ;

Johannessen, Cory M. .

NATURE COMMUNICATIONS, 2017, 8

[3]

Almogy G., 2022, BIORXIV, DOI DOI 10.1101/2022.05.29.493900

[4]

[Anonymous], 2022, Genome analysis toolkit v3.8-1

[5] Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies [J].

Bettegowda, Chetan ;

Sausen, Mark ;

Leary, Rebecca J. ;

Kinde, Isaac ;

Wang, Yuxuan ;

Agrawal, Nishant ;

Bartlett, Bjarne R. ;

Wang, Hao ;

Luber, Brandon ;

Alani, Rhoda M. ;

Antonarakis, Emmanuel S. ;

Azad, Nilofer S. ;

Bardelli, Alberto ;

Brem, Henry ;

Cameron, John L. ;

Lee, Clarence C. ;

Fecher, Leslie A. ;

Gallia, Gary L. ;

Gibbs, Peter ;

Le, Dung ;

Giuntoli, Robert L. ;

Goggins, Michael ;

Hogarty, Michael D. ;

Holdhoff, Matthias ;

Hong, Seung-Mo ;

Jiao, Yuchen ;

Juhl, Hartmut H. ;

Kim, Jenny J. ;

Siravegna, Giulia ;

Laheru, Daniel A. ;

Lauricella, Calogero ;

Lim, Michael ;

Lipson, Evan J. ;

Marie, Suely Kazue Nagahashi ;

Netto, George J. ;

Oliner, Kelly S. ;

Olivi, Alessandro ;

Olsson, Louise ;

Riggins, Gregory J. ;

Sartore-Bianchi, Andrea ;

Schmidt, Kerstin ;

Shih, Ie-Ming ;

Oba-Shinjo, Sueli Mieko ;

Siena, Salvatore ;

Theodorescu, Dan ;

Tie, Jeanne ;

Harkins, Timothy T. ;

Veronese, Silvio ;

Wang, Tian-Li ;

Weingart, Jon D. .

SCIENCE TRANSLATIONAL MEDICINE, 2014, 6 (224)

[6]

Broad Institute, 2019, Picard Toolkit GitHub Repository

[7] High-resolution characterization of sequence signatures due to non-random cleavage of cell-free DNA [J].

Chandrananda, Dineika ;

Thorne, Natalie P. ;

Bahlo, Melanie .

BMC MEDICAL GENOMICS, 2015, 8

[8] Manta: rapid detection of structural variants and indels for germline and cancer sequencing applications [J].

Chen, Xiaoyu ;

Schulz-Trieglaff, Ole ;

Shaw, Richard ;

Barnes, Bret ;

Schlesinger, Felix ;

Kallberg, Morten ;

Cox, Anthony J. ;

Kruglyakl, Semyon ;

Saunders, Christopher T. .

BIOINFORMATICS, 2016, 32 (08) :1220-1222

[9] Detection of low-frequency DNA variants by targeted sequencing of the Watson and Crick strands [J].

Cohen, Joshua D. ;

Douville, Christopher ;

Dudley, Jonathan C. ;

Mog, Brian J. ;

Popoli, Maria ;

Ptak, Janine ;

Dobbyn, Lisa ;

Silliman, Natalie ;

Schaefer, Joy ;

Tie, Jeanne ;

Gibbs, Peter ;

Tomasetti, Cristian ;

Papadopoulos, Nickolas ;

Kinzler, Kenneth W. ;

Vogelstein, Bert .

NATURE BIOTECHNOLOGY, 2021, 39 (10) :1220-+

[10] Detection and localization of surgically resectable cancers with a multi-analyte blood test [J].

Cohen, Joshua D. ;

Li, Lu ;

Wang, Yuxuan ;

Thoburn, Christopher ;

Afsari, Bahman ;

Danilova, Ludmila ;

Douville, Christopher ;

Javed, Ammar A. ;

Wong, Fay ;

Mattox, Austin ;

Hruban, Ralph. H. ;

Wolfgang, Christopher L. ;

Goggins, Michael G. ;

Dal Molin, Marco ;

Wang, Tian-Li ;

Roden, Richard ;

Klein, Alison P. ;

Ptak, Janine ;

Dobbyn, Lisa ;

Schaefer, Joy ;

Silliman, Natalie ;

Popoli, Maria ;

Vogelstein, Joshua T. ;

Browne, James D. ;

Schoen, Robert E. ;

Brand, Randall E. ;

Tie, Jeanne ;

Gibbs, Peter ;

Wong, Hui-Li ;

Mansfield, Aaron S. ;

Jen, Jin ;

Hanash, Samir M. ;

Falconi, Massimo ;

Allen, Peter J. ;

Zhou, Shibin ;

Bettegowda, Chetan ;

Diaz, Luis A., Jr. ;

Tomasetti, Cristian ;

Kinzler, Kenneth W. ;

Vogelstein, Bert ;

Lennon, Anne Marie ;

Papadopoulos, Nickolas .

SCIENCE, 2018, 359 (6378) :926-+

← 1 2 3 4 5 6 7 →