Imperial College London
Alternate

DrRosemaryFisher

Faculty of Medicine, Department of Surgery & Cancer

Honorary Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 3311 1413r.fisher

 
 
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Location

 

Medical OncologyCharing Cross Campus

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Summary

 

Publications

Citation

BibTex format

@article{Maher:2022:10.1038/s41525-022-00297-x,
author = {Maher, G and Fisher, RA and Kaur, B and Aguiar, X and Aravind, P and Cedeno, N and Clark, J and Damon, D and Ghorani, E and Januszewski, A and Kalofonou, F and Murphy, R and Roy, R and Sarwar, N and Openshaw, MR and Seckl, MJ},
doi = {10.1038/s41525-022-00297-x},
journal = {npj Genomic Medicine},
pages = {1--8},
title = {Sensitive screening of single nucleotide polymorphisms in cell free DNA for diagnosis of gestational tumours},
url = {http://dx.doi.org/10.1038/s41525-022-00297-x},
volume = {7},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Maher,G
AU  - Fisher,RA
AU  - Kaur,B
AU  - Aguiar,X
AU  - Aravind,P
AU  - Cedeno,N
AU  - Clark,J
AU  - Damon,D
AU  - Ghorani,E
AU  - Januszewski,A
AU  - Kalofonou,F
AU  - Murphy,R
AU  - Roy,R
AU  - Sarwar,N
AU  - Openshaw,MR
AU  - Seckl,MJ
DO  - 10.1038/s41525-022-00297-x
EP  - 8
PY  - 2022///
SN  - 2056-7944
SP  - 1
TI  - Sensitive screening of single nucleotide polymorphisms in cell free DNA for diagnosis of gestational tumours
T2  - npj Genomic Medicine
UR  - http://dx.doi.org/10.1038/s41525-022-00297-x
UR  - https://www.nature.com/articles/s41525-022-00297-x
UR  - http://hdl.handle.net/10044/1/95132
VL  - 7
ER  -
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