Ultra-Sensitive Mutation Detection and Genome-Wide DNA Copy Number Reconstruction by Error-Corrected Circulating Tumor DNA Sequencing.

Clinical Chemistry
Sonia MansukhaniMarco Gerlinger

Abstract

Circulating free DNA sequencing (cfDNA-Seq) can portray cancer genome landscapes, but highly sensitive and specific technologies are necessary to accurately detect mutations with often low variant frequencies. We developed a customizable hybrid-capture cfDNA-Seq technology using off-the-shelf molecular barcodes and a novel duplex DNA molecule identification tool for enhanced error correction. Modeling based on cfDNA yields from 58 patients showed that this technology, requiring 25 ng of cfDNA, could be applied to >95% of patients with metastatic colorectal cancer (mCRC). cfDNA-Seq of a 32-gene, 163.3-kbp target region detected 100% of single-nucleotide variants, with 0.15% variant frequency in spike-in experiments. Molecular barcode error correction reduced false-positive mutation calls by 97.5%. In 28 consecutively analyzed patients with mCRC, 80 out of 91 mutations previously detected by tumor tissue sequencing were called in the cfDNA. Call rates were similar for point mutations and indels. cfDNA-Seq identified typical mCRC driver mutations in patients in whom biopsy sequencing had failed or did not include key mCRC driver genes. Mutations only called in cfDNA but undetectable in matched biopsies included a subclonal resista...Continue Reading

References

Jun 23, 2006·Nature Methods·Frank DiehlDevin Dressman
Jan 12, 2011·Nature Biotechnology·James T RobinsonJill P Mesirov
May 5, 2012·Nature Protocols·Timour BaslanJames Hicks
Jul 20, 2012·Nature·UNKNOWN Cancer Genome Atlas Network
Dec 1, 2012·Science Translational Medicine·Rebecca J LearyVictor E Velculescu
Mar 15, 2013·The New England Journal of Medicine·Sarah-Jane DawsonNitzan Rosenfeld
Feb 21, 2014·Science Translational Medicine·Chetan BettegowdaLuis A Diaz
May 8, 2014·Cancer Discovery·Daniel A Haber, Victor E Velculescu
Oct 10, 2014·Nature Protocols·Scott R KennedyLawrence A Loeb
Aug 28, 2015·Science Translational Medicine·Isaac Garcia-MurillasNicholas C Turner
Mar 29, 2016·Nature Biotechnology·Aaron M NewmanAsh A Alizadeh
Apr 23, 2016·PLoS Computational Biology·Eric TalevichBoris C Bastian
Oct 12, 2016·Current Protocols in Human Genetics·S A ForbesP J Campbell
Mar 3, 2017·Nature Reviews. Clinical Oncology·Giulia SiravegnaAlberto Bardelli
Apr 7, 2017·BMC Medicine·Samantha Perakis, Michael R Speicher
Apr 27, 2017·Nature·Christopher AbboshCharles Swanton
Aug 18, 2017·Science Translational Medicine·Jillian PhallenVictor E Velculescu
Jan 24, 2018·Annals of Oncology : Official Journal of the European Society for Medical Oncology·S Y MoorcraftN Starling
Feb 21, 2018·Critical Reviews in Oncology/hematology·Shelize KhakooNaureen Starling

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Citations

Dec 13, 2018·Clinical Chemistry·Anjui Wu, Gerhardt Attard
Jul 29, 2019·G3 : Genes - Genomes - Genetics·L Alexander LiggettJames DeGregori
Jul 1, 2020·American Society of Clinical Oncology Educational Book·Catherine C CoombsBrian D Crompton
Sep 5, 2020·Gut·Johann von FeldenAugusto Villanueva
Nov 7, 2018·Cold Spring Harbor Perspectives in Medicine·Elaine R Mardis
Apr 29, 2019·Cell Biology and Toxicology·Diane Catherine Wang, Xiangdong Wang
Nov 2, 2019·Critical Reviews in Clinical Laboratory Sciences·Eleni Tzanikou, Evi Lianidou
Nov 27, 2019·Nature Medicine·Pedram RazaviJorge S Reis-Filho
Jul 10, 2020·Neuro-oncology Advances·Thomas GraillonAnne Barlier
Aug 29, 2019·Nature Reviews. Cancer·Laura Keller, Klaus Pantel
Sep 25, 2020·British Journal of Cancer·Laura KellerKlaus Pantel
Oct 10, 2020·Scientific Reports·Dimitrios KleftogiannisSarah B Ng
Nov 23, 2020·Genes, Chromosomes & Cancer·Angela George, Clare Turnbull
Dec 20, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shelize KhakooDavid Cunningham
Jan 20, 2020·Molecular Aspects of Medicine·Delila Gasi Tandefelt, Johann de Bono
Jun 3, 2021·International Journal of Molecular Sciences·Dariush NasrollahzadehBehnoush Abedi-Ardekani

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