Abstract
| Language | English |
|---|---|
| Article number | 1905 |
| Pages | 1-14 |
| Number of pages | 14 |
| Journal | Cancers |
| Volume | 11 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 29 Nov 2019 |
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Bibliographical note
Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.Keywords
- whole exome sequencing
- Melanoma
- circulating tumour DNA
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Analysis of the whole-exome sequencing of tumor and circulating tumor DNA in metastatic melanoma. / Diefenbach, Russell J.; Lee, Jenny H.; Strbenac, Dario; Yang, Jean Y. H.; Menzies, Alexander M.; Carlino, Matteo S.; Long, Georgina V.; Spillane, Andrew J.; Stretch, Jonathan R.; Saw, Robyn P. M.; Thompson, John F.; Ch'ng, Sydney; Scolyer, Richard A.; Kefford, Richard F.; Rizos, Helen.
In: Cancers, Vol. 11, No. 12, 1905, 29.11.2019, p. 1-14.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Analysis of the whole-exome sequencing of tumor and circulating tumor DNA in metastatic melanoma
AU - Diefenbach, Russell J.
AU - Lee, Jenny H.
AU - Strbenac, Dario
AU - Yang, Jean Y. H.
AU - Menzies, Alexander M.
AU - Carlino, Matteo S.
AU - Long, Georgina V.
AU - Spillane, Andrew J.
AU - Stretch, Jonathan R.
AU - Saw, Robyn P. M.
AU - Thompson, John F.
AU - Ch'ng, Sydney
AU - Scolyer, Richard A.
AU - Kefford, Richard F.
AU - Rizos, Helen
N1 - Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
PY - 2019/11/29
Y1 - 2019/11/29
N2 - The use of circulating tumor DNA (ctDNA) to monitor cancer progression and response to therapy has significant potential but there is only limited data on whether this technique can detect the presence of low frequency subclones that may ultimately confer therapy resistance. In this study, we sought to evaluate whether whole-exome sequencing (WES) of ctDNA could accurately profile the mutation landscape of metastatic melanoma. We used WES to identify variants in matched, tumor-derived genomic DNA (gDNA) and plasma-derived ctDNA isolated from a cohort of 10 metastatic cutaneous melanoma patients. WES parameters such as sequencing coverage and total sequencing reads were comparable between gDNA and ctDNA. The mutant allele frequency of common single nucleotide variants was lower in ctDNA, reflecting the lower read depth and minor fraction of ctDNA within the total circulating free DNA pool. There was also variable concordance between gDNA and ctDNA based on the total number and identity of detected variants and this was independent of the tumor biopsy site. Nevertheless, established melanoma driver mutations and several other melanoma-associated mutations were concordant between matched gDNA and ctDNA. This study highlights that WES of ctDNA could capture clinically relevant mutations present in melanoma metastases and that enhanced sequencing sensitivity will be required to identify low frequency mutations.
AB - The use of circulating tumor DNA (ctDNA) to monitor cancer progression and response to therapy has significant potential but there is only limited data on whether this technique can detect the presence of low frequency subclones that may ultimately confer therapy resistance. In this study, we sought to evaluate whether whole-exome sequencing (WES) of ctDNA could accurately profile the mutation landscape of metastatic melanoma. We used WES to identify variants in matched, tumor-derived genomic DNA (gDNA) and plasma-derived ctDNA isolated from a cohort of 10 metastatic cutaneous melanoma patients. WES parameters such as sequencing coverage and total sequencing reads were comparable between gDNA and ctDNA. The mutant allele frequency of common single nucleotide variants was lower in ctDNA, reflecting the lower read depth and minor fraction of ctDNA within the total circulating free DNA pool. There was also variable concordance between gDNA and ctDNA based on the total number and identity of detected variants and this was independent of the tumor biopsy site. Nevertheless, established melanoma driver mutations and several other melanoma-associated mutations were concordant between matched gDNA and ctDNA. This study highlights that WES of ctDNA could capture clinically relevant mutations present in melanoma metastases and that enhanced sequencing sensitivity will be required to identify low frequency mutations.
KW - whole exome sequencing
KW - Melanoma
KW - circulating tumour DNA
UR - http://purl.org/au-research/grants/nhmrc/1093017
UR - http://purl.org/au-research/grants/nhmrc/1128951
UR - http://purl.org/au-research/grants/nhmrc/1104503
UR - http://purl.org/au-research/grants/nhmrc/1141295
UR - http://purl.org/au-research/grants/nhmrc/1119059
UR - http://www.scopus.com/inward/record.url?scp=85076053404&partnerID=8YFLogxK
U2 - 10.3390/cancers11121905
DO - 10.3390/cancers11121905
M3 - Article
VL - 11
SP - 1
EP - 14
JO - Cancers
T2 - Cancers
JF - Cancers
SN - 2072-6694
IS - 12
M1 - 1905
ER -