Till sidans topp

Sidansvarig: Webbredaktion
Sidan uppdaterades: 2012-09-11 15:12

Tipsa en vän
Utskriftsversion

Serial Next-Generation Se… - Göteborgs universitet Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

Serial Next-Generation Sequencing of Circulating Cell-Free DNA Evaluating Tumor Clone Response To Molecularly Targeted Drug Administration.

Artikel i vetenskaplig tidskrift
Författare Jean Sebastien Frenel
Suzanne Carreira
Jane Goodall
Desam Roda
Raquel Perez-Lopez
Nina Tunariu
Ruth Riisnaes
Susana Miranda
Ines Figueiredo
Daniel Nava-Rodrigues
Alan Smith
Christophe Leux
Isaac Garcia-Murillas
Roberta Ferraldeschi
David Lorente
Joaquin Mateo
Michael Ong
Timothy A Yap
Udai Banerji
Delila Gasi Tandefelt
Nick Turner
Gerhardt Attard
Johann S de Bono
Publicerad i Clinical cancer research : an official journal of the American Association for Cancer Research
Volym 21
Nummer/häfte 20
Sidor 4586-96
ISSN 1078-0432
Publiceringsår 2015
Publicerad vid
Sidor 4586-96
Språk en
Länkar dx.doi.org/10.1158/1078-0432.CCR-15...
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämnesord Adult, Aged, Biomarkers, Tumor, genetics, DNA, Complementary, genetics, DNA, Neoplasm, genetics, Disease Progression, Female, High-Throughput Nucleotide Sequencing, methods, Humans, Male, Middle Aged, Mutation, genetics, Neoplastic Cells, Circulating, pathology, Phosphatidylinositol 3-Kinases, genetics, Proto-Oncogene Proteins c-akt, genetics, TOR Serine-Threonine Kinases, genetics, ras Proteins, genetics
Ämneskategorier Klinisk medicin

Sammanfattning

We evaluated whether next-generation sequencing (NGS) of circulating cell-free DNA (cfDNA) could be used for patient selection and as a tumor clone response biomarker in patients with advanced cancers participating in early-phase clinical trials of targeted drugs.Plasma samples from patients with known tumor mutations who completed at least two courses of investigational targeted therapy were collected monthly, until disease progression. NGS was performed sequentially on the Ion Torrent PGM platform.cfDNA was extracted from 39 patients with various tumor types. Treatments administered targeted mainly the PI3K-AKT-mTOR pathway (n = 28) or MEK (n = 7). Overall, 159 plasma samples were sequenced with a mean sequencing coverage achieved of 1,685X across experiments. At trial initiation (C1D1), 23 of 39 (59%) patients had at least one mutation identified in cfDNA (mean 2, range 1-5). Out of the 44 mutations identified at C1D1, TP53, PIK3CA and KRAS were the top 3 mutated genes identified, with 18 (41%), 9 (20%), 8 (18%) different mutations, respectively. Out of these 23 patients, 13 received a targeted drug matching their tumor profile. For the 23 patients with cfDNA mutation at C1D1, the monitoring of mutation allele frequency (AF) in consecutive plasma samples during treatment with targeted drugs demonstrated potential treatment associated clonal responses. Longitudinal monitoring of cfDNA samples with multiple mutations indicated the presence of separate clones behaving discordantly. Molecular changes at cfDNA mutation level were associated with time to disease progression by RECIST criteria.Targeted NGS of cfDNA has potential clinical utility to monitor the delivery of targeted therapies.

Sidansvarig: Webbredaktion|Sidan uppdaterades: 2012-09-11
Dela:

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?