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Sensitive screening of single nucleotide polymorphisms in cell free DNA for diagnosis of gestational tumours

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Title: Sensitive screening of single nucleotide polymorphisms in cell free DNA for diagnosis of gestational tumours
Authors: Maher, G
Fisher, RA
Kaur, B
Aguiar, X
Aravind, P
Cedeno, N
Clark, J
Damon, D
Ghorani, E
Januszewski, A
Kalofonou, F
Murphy, R
Roy, R
Sarwar, N
Openshaw, MR
Seckl, MJ
Item Type: Journal Article
Abstract: Tumours expressing human chorionic gonadotropin (hCG), the majority of which are difficult to biopsy due to their vascularity, have disparate prognoses depending on their origin. As optimal management relies on accurate diagnosis, we aimed to develop a sensitive cell free DNA (cfDNA) assay to non-invasively distinguish between cases of gestational and non-gestational origin. Deep error-corrected Illumina sequencing of 195 common single nucleotide polymorphisms (SNPs) in cfDNA and matched genomic DNA from 36 patients with hCG-secreting tumours (serum hCG 5 to 3,042,881 IU/L) and 7 controls with normal hCG levels (≤ 4 IU/L) was performed. cfDNA from confirmed gestational tumours with hCG levels ranging from 1,497 to 700,855 IU/L had multiple (n ≥12) ‘non-host’ alleles (i.e. alleles of paternal origin). In such cases the non-host fraction of cfDNA ranged from 0.3% - 40.4% and correlated with serum hCG levels. At lower hCG levels the ability to detect non-host cfDNA was variable, with the detection limit dependent on the type of causative pregnancy. Patients with non-gestational tumours were identifiable by the absence of non-host cfDNA, with copy number alterations detectable in the majority of cases. Following validation in a larger cohort, our sensitive assay will enable clinicians to better inform patients, for whom biopsy is inappropriate, of their prognosis and provide optimum management.
Issue Date: 8-Apr-2022
Date of Acceptance: 4-Feb-2022
URI: http://hdl.handle.net/10044/1/95132
DOI: 10.1038/s41525-022-00297-x
ISSN: 2056-7944
Publisher: Nature Research
Start Page: 1
End Page: 8
Journal / Book Title: npj Genomic Medicine
Volume: 7
Issue: 26
Copyright Statement: © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: Rosetrees Trust
Funder's Grant Number: Seedcorn 2020\100003
Publication Status: Published
Online Publication Date: 2022-04-08
Appears in Collections:Department of Surgery and Cancer
Faculty of Medicine



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