Mutational landscape of plasma cell-free DNA identifies molecular features associated with therapeutic response in patients with colon cancer. A pilot study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F21%3A00551989" target="_blank" >RIV/68378041:_____/21:00551989 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064190:_____/21:N0000032 RIV/00216208:11140/21:10429187 RIV/00216208:11110/21:10429187 RIV/00064165:_____/21:10429187

Výsledek na webu

<a href="https://academic.oup.com/mutage/article-abstract/36/5/358/6313214?redirectedFrom=fulltext" target="_blank" >https://academic.oup.com/mutage/article-abstract/36/5/358/6313214?redirectedFrom=fulltext</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/mutage/geab024" target="_blank" >10.1093/mutage/geab024</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Mutational landscape of plasma cell-free DNA identifies molecular features associated with therapeutic response in patients with colon cancer. A pilot study

Popis výsledku v původním jazyce

Cell-free DNA (cfDNA) has recently been used as a non-invasive diagnostic tool for detecting tumour-specific mutations. cfDNA may also be used for monitoring disease progression and treatment response, but so far researchers focused on one or few genes only. A genomic profile may provide better information on patient prognosis compared to single specific mutations.nIn this hypothesis-generating study, we profiled by whole exome sequencing serial plasma samples from 10 colon cancer (CC) patients collected before and after 5-fluorouracil-based therapy, and one year after diagnosis to determine alterations associated with treatment response. In parallel, genome profiling was also performed in patients' corresponding tumour tissue to ascertain the molecular landscape of resistant tumours.nThe mutation concordance between cfDNA and tumour tissue DNA was higher in more advanced tumour stages than in the early stages of the disease. In non-responders, a specific mutation profile was observed in tumour tissues (TPSD1 p.Ala92Thr, CPAMD8 p.Arg341Gln, OBP2A p.ArgTyr123CysHis). A pathogenic APC mutation (p.Ser1315Ter) was detected only in cfDNA of one poor responder one year after the diagnosis and after therapy termination. Another poor responder presented a likely pathogenic TP53 mutation (p.Arg110Pro) in cfDNA of all plasma samplings and in tumour tissue.nIn conclusion, cfDNA could be used for genetic characterisation of CC patients and might be clinically useful for non-invasive therapy response monitoring.

Název v anglickém jazyce

Mutational landscape of plasma cell-free DNA identifies molecular features associated with therapeutic response in patients with colon cancer. A pilot study

Popis výsledku anglicky

Cell-free DNA (cfDNA) has recently been used as a non-invasive diagnostic tool for detecting tumour-specific mutations. cfDNA may also be used for monitoring disease progression and treatment response, but so far researchers focused on one or few genes only. A genomic profile may provide better information on patient prognosis compared to single specific mutations.nIn this hypothesis-generating study, we profiled by whole exome sequencing serial plasma samples from 10 colon cancer (CC) patients collected before and after 5-fluorouracil-based therapy, and one year after diagnosis to determine alterations associated with treatment response. In parallel, genome profiling was also performed in patients' corresponding tumour tissue to ascertain the molecular landscape of resistant tumours.nThe mutation concordance between cfDNA and tumour tissue DNA was higher in more advanced tumour stages than in the early stages of the disease. In non-responders, a specific mutation profile was observed in tumour tissues (TPSD1 p.Ala92Thr, CPAMD8 p.Arg341Gln, OBP2A p.ArgTyr123CysHis). A pathogenic APC mutation (p.Ser1315Ter) was detected only in cfDNA of one poor responder one year after the diagnosis and after therapy termination. Another poor responder presented a likely pathogenic TP53 mutation (p.Arg110Pro) in cfDNA of all plasma samplings and in tumour tissue.nIn conclusion, cfDNA could be used for genetic characterisation of CC patients and might be clinically useful for non-invasive therapy response monitoring.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10603 - Genetics and heredity (medical genetics to be 3)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Mutagenesis

ISSN

0267-8357

e-ISSN

1464-3804

Svazek periodika

36

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

358-368

Kód UT WoS článku

000709415400004

EID výsledku v databázi Scopus

2-s2.0-85118096223