Detection of rare mutations, copy number alterations, and methylation in the same template DNA molecules.
Wang, Y
Douville, C
Cohen, JD
Mattox, A
Curtis, S
Silliman, N
Popoli, M
Ptak, J
Dobbyn, L
Nehme, N
Dudley, JC
Summers, M
Zhang, M
Ho-Pham, LT
Tran, BNH
Tran, TS
Nguyen, TV
Bettegowda, C
Papadopoulos, N
Kinzler, KW
Vogelstein, B
- Publisher:
- NATL ACAD SCIENCES
- Publication Type:
- Journal Article
- Citation:
- Proc Natl Acad Sci U S A, 2023, 120, (15), pp. e2220704120
- Issue Date:
- 2023-04-11
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Wang, Y | |
dc.contributor.author | Douville, C | |
dc.contributor.author | Cohen, JD | |
dc.contributor.author | Mattox, A | |
dc.contributor.author | Curtis, S | |
dc.contributor.author | Silliman, N | |
dc.contributor.author | Popoli, M | |
dc.contributor.author | Ptak, J | |
dc.contributor.author | Dobbyn, L | |
dc.contributor.author | Nehme, N | |
dc.contributor.author | Dudley, JC | |
dc.contributor.author | Summers, M | |
dc.contributor.author | Zhang, M | |
dc.contributor.author | Ho-Pham, LT | |
dc.contributor.author | Tran, BNH | |
dc.contributor.author | Tran, TS | |
dc.contributor.author | Nguyen, TV | |
dc.contributor.author | Bettegowda, C | |
dc.contributor.author | Papadopoulos, N | |
dc.contributor.author | Kinzler, KW | |
dc.contributor.author | Vogelstein, B | |
dc.date.accessioned | 2024-02-27T06:43:33Z | |
dc.date.available | 2024-02-27T06:43:33Z | |
dc.date.issued | 2023-04-11 | |
dc.identifier.citation | Proc Natl Acad Sci U S A, 2023, 120, (15), pp. e2220704120 | |
dc.identifier.issn | 0027-8424 | |
dc.identifier.issn | 1091-6490 | |
dc.identifier.uri | http://hdl.handle.net/10453/175904 | |
dc.description.abstract | The analysis of cell-free DNA (cfDNA) from plasma offers great promise for the earlier detection of cancer. At present, changes in DNA sequence, methylation, or copy number are the most sensitive ways to detect the presence of cancer. To further increase the sensitivity of such assays with limited amounts of sample, it would be useful to be able to evaluate the same template molecules for all these changes. Here, we report an approach, called MethylSaferSeqS, that achieves this goal, and can be applied to any standard library preparation method suitable for massively parallel sequencing. The innovative step was to copy both strands of each DNA-barcoded molecule with a primer that allows the subsequent separation of the original strands (retaining their 5-methylcytosine residues) from the copied strands (in which the 5-methylcytosine residues are replaced with unmodified cytosine residues). The epigenetic and genetic alterations present in the DNA molecules can then be obtained from the original and copied strands, respectively. We applied this approach to plasma from 265 individuals, including 198 with cancers of the pancreas, ovary, lung, and colon, and found the expected patterns of mutations, copy number alterations, and methylation. Furthermore, we could determine which original template DNA molecules were methylated and/or mutated. MethylSaferSeqS should be useful for addressing a variety of questions relating genetics and epigenetics. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.publisher | NATL ACAD SCIENCES | |
dc.relation.ispartof | Proc Natl Acad Sci U S A | |
dc.relation.isbasedon | 10.1073/pnas.2220704120 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject.mesh | Female | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Methylation | |
dc.subject.mesh | DNA Copy Number Variations | |
dc.subject.mesh | 5-Methylcytosine | |
dc.subject.mesh | DNA | |
dc.subject.mesh | Mutation | |
dc.subject.mesh | Neoplasms | |
dc.subject.mesh | DNA Methylation | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Neoplasms | |
dc.subject.mesh | 5-Methylcytosine | |
dc.subject.mesh | DNA | |
dc.subject.mesh | DNA Methylation | |
dc.subject.mesh | Methylation | |
dc.subject.mesh | Mutation | |
dc.subject.mesh | Female | |
dc.subject.mesh | DNA Copy Number Variations | |
dc.subject.mesh | Female | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Methylation | |
dc.subject.mesh | DNA Copy Number Variations | |
dc.subject.mesh | 5-Methylcytosine | |
dc.subject.mesh | DNA | |
dc.subject.mesh | Mutation | |
dc.subject.mesh | Neoplasms | |
dc.subject.mesh | DNA Methylation | |
dc.title | Detection of rare mutations, copy number alterations, and methylation in the same template DNA molecules. | |
dc.type | Journal Article | |
utslib.citation.volume | 120 | |
utslib.location.activity | United States | |
pubs.organisational-group | University of Technology Sydney | |
pubs.organisational-group | University of Technology Sydney/Faculty of Engineering and Information Technology | |
pubs.organisational-group | University of Technology Sydney/Strength - CHT - Health Technologies | |
pubs.organisational-group | University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering | |
pubs.organisational-group | University of Technology Sydney/Centre for Health Technologies (CHT) | |
utslib.copyright.status | open_access | * |
dc.date.updated | 2024-02-27T06:43:30Z | |
pubs.issue | 15 | |
pubs.publication-status | Published | |
pubs.volume | 120 | |
utslib.citation.issue | 15 |
Abstract:
The analysis of cell-free DNA (cfDNA) from plasma offers great promise for the earlier detection of cancer. At present, changes in DNA sequence, methylation, or copy number are the most sensitive ways to detect the presence of cancer. To further increase the sensitivity of such assays with limited amounts of sample, it would be useful to be able to evaluate the same template molecules for all these changes. Here, we report an approach, called MethylSaferSeqS, that achieves this goal, and can be applied to any standard library preparation method suitable for massively parallel sequencing. The innovative step was to copy both strands of each DNA-barcoded molecule with a primer that allows the subsequent separation of the original strands (retaining their 5-methylcytosine residues) from the copied strands (in which the 5-methylcytosine residues are replaced with unmodified cytosine residues). The epigenetic and genetic alterations present in the DNA molecules can then be obtained from the original and copied strands, respectively. We applied this approach to plasma from 265 individuals, including 198 with cancers of the pancreas, ovary, lung, and colon, and found the expected patterns of mutations, copy number alterations, and methylation. Furthermore, we could determine which original template DNA molecules were methylated and/or mutated. MethylSaferSeqS should be useful for addressing a variety of questions relating genetics and epigenetics.
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