Clinical-grade validation of whole genome sequencing reveals robust detection of low-frequency variants and copy number alterations in CLL
(2018) In British Journal of Haematology 182(3). p.412-417- Abstract
The 100 000 Genome Project aims to develop a diagnostics platform by introducing whole genome sequencing (WGS) into clinical practice. Samples from patients with chronic lymphocytic leukaemia were subjected to WGS. WGS detection of single nucleotide variants and insertion/deletions were validated by targeted next generation sequencing showing high concordance (96·3%), also for detection of sub-clonal variants and low-frequency TP53 variants. Copy number alteration detection was verified by fluorescent in situ hybridisation and genome-wide single nucleotide polymorphism array (concordances of 86·7% and 92·9%, respectively), confirming adequate sensitivity by WGS. Our results confirm that WGS can provide comprehensive genomic... (More)
The 100 000 Genome Project aims to develop a diagnostics platform by introducing whole genome sequencing (WGS) into clinical practice. Samples from patients with chronic lymphocytic leukaemia were subjected to WGS. WGS detection of single nucleotide variants and insertion/deletions were validated by targeted next generation sequencing showing high concordance (96·3%), also for detection of sub-clonal variants and low-frequency TP53 variants. Copy number alteration detection was verified by fluorescent in situ hybridisation and genome-wide single nucleotide polymorphism array (concordances of 86·7% and 92·9%, respectively), confirming adequate sensitivity by WGS. Our results confirm that WGS can provide comprehensive genomic characterisation for clinical trials, drug discovery and, ultimately, precision medicine.
(Less)
- author
- publishing date
- 2018-05-29
- type
- Contribution to journal
- publication status
- published
- subject
- in
- British Journal of Haematology
- volume
- 182
- issue
- 3
- pages
- 412 - 417
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:29808933
- scopus:85047731241
- ISSN
- 0007-1048
- DOI
- 10.1111/bjh.15406
- language
- English
- LU publication?
- no
- id
- de866cb3-efb0-422f-b53a-04fa6f027668
- date added to LUP
- 2018-11-12 06:04:23
- date last changed
- 2024-08-06 02:59:53
@article{de866cb3-efb0-422f-b53a-04fa6f027668, abstract = {{<p>The 100 000 Genome Project aims to develop a diagnostics platform by introducing whole genome sequencing (WGS) into clinical practice. Samples from patients with chronic lymphocytic leukaemia were subjected to WGS. WGS detection of single nucleotide variants and insertion/deletions were validated by targeted next generation sequencing showing high concordance (96·3%), also for detection of sub-clonal variants and low-frequency TP53 variants. Copy number alteration detection was verified by fluorescent in situ hybridisation and genome-wide single nucleotide polymorphism array (concordances of 86·7% and 92·9%, respectively), confirming adequate sensitivity by WGS. Our results confirm that WGS can provide comprehensive genomic characterisation for clinical trials, drug discovery and, ultimately, precision medicine.</p>}}, author = {{Klintman, Jenny and Barmpouti, Katerina and Knight, Samantha J L and Robbe, Pauline and Dreau, Hélène and Clifford, Ruth and Ridout, Kate and Burns, Adam and Timbs, Adele and Bruce, David and Antoniou, Pavlos and Sosinsky, Alona and Becq, Jennifer and Bentley, David and Hillmen, Peter and Taylor, Jenny C and Caulfield, Mark and Schuh, Anna H}}, issn = {{0007-1048}}, language = {{eng}}, month = {{05}}, number = {{3}}, pages = {{412--417}}, publisher = {{Wiley-Blackwell}}, series = {{British Journal of Haematology}}, title = {{Clinical-grade validation of whole genome sequencing reveals robust detection of low-frequency variants and copy number alterations in CLL}}, url = {{http://dx.doi.org/10.1111/bjh.15406}}, doi = {{10.1111/bjh.15406}}, volume = {{182}}, year = {{2018}}, }