Detection of genomic alterations in breast cancer with circulating tumour DNA sequencing.

Autor:	Kleftogiannis D; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore, 138672, Singapore., Ho D; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore, 138672, Singapore.; Division of Medical Oncology, National Cancer Centre Singapore (NCCS), Singapore, 169610, Singapore., Liew JX; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore, 138672, Singapore., Poon PSY; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore, 138672, Singapore., Gan A; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore, 138672, Singapore., Ng RC; Division of Medical Oncology, National Cancer Centre Singapore (NCCS), Singapore, 169610, Singapore., Tan BK; Department of General Surgery, Singapore General Hospital (SGH), Singapore, 169608, Singapore.; Division of Surgical Oncology, National Cancer Centre Singapore (NCCS), Singapore, 169610, Singapore.; Department of General Surgery, Sengkang General Hospital, Singapore, 544886, Singapore., Tay KH; Vascular and Interventional Radiology Department, Singapore General Hospital (SGH), Singapore, 169608, Singapore., Lim SH; KK Breast Centre, Kandang Kerbau Women's and Children's Hospital, Singapore, 229899, Singapore., Tan GS; Department of Anatomical Pathology and Translational Pathology Centre, Singapore General Hospital (SGH), Singapore, 169608, Singapore., Shih CC; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore, 138672, Singapore., Lim TK; Department of Anatomical Pathology and Translational Pathology Centre, Singapore General Hospital (SGH), Singapore, 169608, Singapore., Lee AS; Division of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore (NCCS), Singapore, 169610, Singapore.; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, 117597, Singapore.; SingHealth Duke-NUS Oncology Academic Clinical Programme (ONCO ACP), Duke-NUS Medical School, Singapore, 169857, Singapore., Tan IB; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore, 138672, Singapore.; Division of Medical Oncology, National Cancer Centre Singapore (NCCS), Singapore, 169610, Singapore.; SingHealth Duke-NUS Oncology Academic Clinical Programme (ONCO ACP), Duke-NUS Medical School, Singapore, 169857, Singapore., Yap YS; Division of Medical Oncology, National Cancer Centre Singapore (NCCS), Singapore, 169610, Singapore. yap.yoon.sim@singhealth.com.sg.; SingHealth Duke-NUS Oncology Academic Clinical Programme (ONCO ACP), Duke-NUS Medical School, Singapore, 169857, Singapore. yap.yoon.sim@singhealth.com.sg., Ng SB; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore, 138672, Singapore. ngbhs@gis.a-star.edu.sg.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2020 Oct 08; Vol. 10 (1), pp. 16774. Date of Electronic Publication: 2020 Oct 08.
DOI:	10.1038/s41598-020-72818-6
Abstrakt:	Analysis of circulating cell-free DNA (cfDNA) has opened new opportunities for characterizing tumour mutational landscapes with many applications in genomic-driven oncology. We developed a customized targeted cfDNA sequencing approach for breast cancer (BC) using unique molecular identifiers (UMIs) for error correction. Our assay, spanning a 284.5 kb target region, is combined with a novel freely-licensed bioinformatics pipeline that provides detection of low-frequency variants, and reliable identification of copy number variations (CNVs) directly from plasma DNA. We first evaluated our pipeline on reference samples. Then in a cohort of 35 BC patients our approach detected actionable driver and clonal variants at low variant frequency levels in cfDNA that were concordant (77%) with sequencing of primary and/or metastatic solid tumour sites. We also detected ERRB2 gene CNVs used for HER2 subtype classification with 80% precision compared to immunohistochemistry. Further, we evaluated fragmentation profiles of cfDNA in BC and observed distinct differences compared to data from healthy individuals. Our results show that the developed assay addresses the majority of tumour associated aberrations directly from plasma DNA, and thus may be used to elucidate genomic alterations in liquid biopsy studies.
Databáze:	MEDLINE
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