Fragment Length of Circulating Tumor DNA.
Malignant tumors shed DNA into the circulation. The transient half-life of circulating tumor DNA (ctDNA) may afford the opportunity to diagnose, monitor recurrence, and evaluate response to therapy solely through a non-invasive blood draw. However, detecting ctDNA against the normally occurring back...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-07-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006162&type=printable |
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| author | Hunter R Underhill Jacob O Kitzman Sabine Hellwig Noah C Welker Riza Daza Daniel N Baker Keith M Gligorich Robert C Rostomily Mary P Bronner Jay Shendure |
| author_facet | Hunter R Underhill Jacob O Kitzman Sabine Hellwig Noah C Welker Riza Daza Daniel N Baker Keith M Gligorich Robert C Rostomily Mary P Bronner Jay Shendure |
| author_sort | Hunter R Underhill |
| collection | DOAJ |
| description | Malignant tumors shed DNA into the circulation. The transient half-life of circulating tumor DNA (ctDNA) may afford the opportunity to diagnose, monitor recurrence, and evaluate response to therapy solely through a non-invasive blood draw. However, detecting ctDNA against the normally occurring background of cell-free DNA derived from healthy cells has proven challenging, particularly in non-metastatic solid tumors. In this study, distinct differences in fragment length size between ctDNAs and normal cell-free DNA are defined. Human ctDNA in rat plasma derived from human glioblastoma multiforme stem-like cells in the rat brain and human hepatocellular carcinoma in the rat flank were found to have a shorter principal fragment length than the background rat cell-free DNA (134-144 bp vs. 167 bp, respectively). Subsequently, a similar shift in the fragment length of ctDNA in humans with melanoma and lung cancer was identified compared to healthy controls. Comparison of fragment lengths from cell-free DNA between a melanoma patient and healthy controls found that the BRAF V600E mutant allele occurred more commonly at a shorter fragment length than the fragment length of the wild-type allele (132-145 bp vs. 165 bp, respectively). Moreover, size-selecting for shorter cell-free DNA fragment lengths substantially increased the EGFR T790M mutant allele frequency in human lung cancer. These findings provide compelling evidence that experimental or bioinformatic isolation of a specific subset of fragment lengths from cell-free DNA may improve detection of ctDNA. |
| format | Article |
| id | doaj-art-51be2cc80ef6462197e8973b01295358 |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2016-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-51be2cc80ef6462197e8973b012953582025-08-20T02:03:35ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042016-07-01127e100616210.1371/journal.pgen.1006162Fragment Length of Circulating Tumor DNA.Hunter R UnderhillJacob O KitzmanSabine HellwigNoah C WelkerRiza DazaDaniel N BakerKeith M GligorichRobert C RostomilyMary P BronnerJay ShendureMalignant tumors shed DNA into the circulation. The transient half-life of circulating tumor DNA (ctDNA) may afford the opportunity to diagnose, monitor recurrence, and evaluate response to therapy solely through a non-invasive blood draw. However, detecting ctDNA against the normally occurring background of cell-free DNA derived from healthy cells has proven challenging, particularly in non-metastatic solid tumors. In this study, distinct differences in fragment length size between ctDNAs and normal cell-free DNA are defined. Human ctDNA in rat plasma derived from human glioblastoma multiforme stem-like cells in the rat brain and human hepatocellular carcinoma in the rat flank were found to have a shorter principal fragment length than the background rat cell-free DNA (134-144 bp vs. 167 bp, respectively). Subsequently, a similar shift in the fragment length of ctDNA in humans with melanoma and lung cancer was identified compared to healthy controls. Comparison of fragment lengths from cell-free DNA between a melanoma patient and healthy controls found that the BRAF V600E mutant allele occurred more commonly at a shorter fragment length than the fragment length of the wild-type allele (132-145 bp vs. 165 bp, respectively). Moreover, size-selecting for shorter cell-free DNA fragment lengths substantially increased the EGFR T790M mutant allele frequency in human lung cancer. These findings provide compelling evidence that experimental or bioinformatic isolation of a specific subset of fragment lengths from cell-free DNA may improve detection of ctDNA.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006162&type=printable |
| spellingShingle | Hunter R Underhill Jacob O Kitzman Sabine Hellwig Noah C Welker Riza Daza Daniel N Baker Keith M Gligorich Robert C Rostomily Mary P Bronner Jay Shendure Fragment Length of Circulating Tumor DNA. PLoS Genetics |
| title | Fragment Length of Circulating Tumor DNA. |
| title_full | Fragment Length of Circulating Tumor DNA. |
| title_fullStr | Fragment Length of Circulating Tumor DNA. |
| title_full_unstemmed | Fragment Length of Circulating Tumor DNA. |
| title_short | Fragment Length of Circulating Tumor DNA. |
| title_sort | fragment length of circulating tumor dna |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006162&type=printable |
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