Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/16890
Title: Digital PCR of genomic rearrangements for monitoring circulating tumour DNA
Austin Authors: Do, Hongdo;Cameron, Daniel;Molania, Ramyar;Thapa, Bibhusal ;Rivall, Gareth;Mitchell, Paul L R ;Murone, Carmel ;John, Thomas ;Papenfuss, Anthony;Dobrovic, Alexander 
Affiliation: Department of Medical Oncology, Austin Health, Heidelberg, Victoria, Australia
Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Department of Pathology, University of Melbourne, Parkville, Victoria, Australia
School of Cancer Medicine, La Trobe University, Bundoora, Victoria, Australia
Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville,Victoria, Australia
Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia
Translational Genomics and Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Department of Medicine, The University of Melbourne, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Bundoora,Victoria Australia
Department of Pathology, University of Melbourne, Parkville, Victoria, Australia
Issue Date: 18-Oct-2016
Publication information: Advances in Experimental Medicine and Biology 2016; 924:139-146
Abstract: Identifying circulating tumour DNA (ctDNA) for monitoring of cancer therapy is dependent on the development of readily designed, sensitive cancer-specific DNA markers. Genomic rearrangements that are present in the vast majority of cancers provide such markers.Tumour DNA isolated from two fresh-frozen lung tumours underwent whole genome sequencing. Genomic rearrangements were detected using a new computational algorithm, GRIDSS. Four genomic rearrangements from each tumour were chosen for further study using rearrangement-specific primers. Six of the eight rearrangements tested were identified as tumour-specific, the remaining two were present in the germline. ctDNA was quantified using digital PCR for the tumour genomic rearrangements in patient blood. Interestingly, one of the patients had no detectable ctDNA either prior to or post surgery although the rearrangements were readily detectable in the tumour DNA.This study demonstrates the feasibility of using digital PCR based on genomic rearrangements for the monitoring of minimal residual disease. In addition, whole genome sequencing provided further information enabling therapeutic choices including the identification of a cryptic EGFR exon 19 deletion in one patient and the identification of a high somatic mutation load in the other patient. This approach can be used as a model for all cancers with rearranged genomes.
URI: http://ahro.austin.org.au/austinjspui/handle/1/16890
DOI: 10.1007/978-3-319-42044-8_27
ORCID: 0000-0003-3414-112X
PubMed URL: https://pubmed.ncbi.nlm.nih.gov/27753035
Type: Journal Article
Subjects: Droplet digital PCR
Genomic rearrangement
Liquid biopsy
Lung cancer
Whole genome sequencing
Appears in Collections:Journal articles

Show full item record

Page view(s)

4
checked on Nov 28, 2022

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.