Cargando…

MLH1 single-nucleotide variant in circulating tumor DNA predicts overall survival of patients with hepatocellular carcinoma

Liquid biopsy can provide a strong basis for precision medicine. We aimed to identify novel single-nucleotide variants (SNVs) in circulating tumor DNA (ctDNA) in patients with hepatocellular carcinoma (HCC). Deep sequencing of plasma-derived ctDNA from 59 patients with HCC was performed using a pane...

Descripción completa

Detalles Bibliográficos
Autores principales: Kim, Soon Sun, Eun, Jung Woo, Choi, Ji-Hye, Woo, Hyun Goo, Cho, Hyo Jung, Ahn, Hye Ri, Suh, Chul Won, Baek, Geum Ok, Cho, Sung Won, Cheong, Jae Youn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576198/
https://www.ncbi.nlm.nih.gov/pubmed/33082400
http://dx.doi.org/10.1038/s41598-020-74494-y
_version_ 1783597968328228864
author Kim, Soon Sun
Eun, Jung Woo
Choi, Ji-Hye
Woo, Hyun Goo
Cho, Hyo Jung
Ahn, Hye Ri
Suh, Chul Won
Baek, Geum Ok
Cho, Sung Won
Cheong, Jae Youn
author_facet Kim, Soon Sun
Eun, Jung Woo
Choi, Ji-Hye
Woo, Hyun Goo
Cho, Hyo Jung
Ahn, Hye Ri
Suh, Chul Won
Baek, Geum Ok
Cho, Sung Won
Cheong, Jae Youn
author_sort Kim, Soon Sun
collection PubMed
description Liquid biopsy can provide a strong basis for precision medicine. We aimed to identify novel single-nucleotide variants (SNVs) in circulating tumor DNA (ctDNA) in patients with hepatocellular carcinoma (HCC). Deep sequencing of plasma-derived ctDNA from 59 patients with HCC was performed using a panel of 2924 SNVs in 69 genes. In 55.9% of the patients, at least one somatic mutation was detected. Among 25 SNVs in 12 genes, four frequently observed SNVs, MLH1 (13%), STK11 (13%), PTEN (9%), and CTNNB1 (4%), were validated using droplet digital polymerase chain reaction with ctDNA from 62 patients with HCC. Three candidate SNVs were detected in 35.5% of the patients, with a frequency of 19% for MLH1 chr3:37025749T>A, 11% for STK11 chr19:1223126C>G, and 8% for PTEN chr10:87864461C>G. The MLH1 and STK11 SNVs were also confirmed in HCC tissues. The presence of the MLH1 SNV, in combination with an increased ctDNA level, predicted poor overall survival among 107 patients. MLH1 chr3:37025749T>A SNV detection in ctDNA is feasible, and thus, ctDNA can be used to detect somatic mutations in HCC. Furthermore, the presence or absence of the MLH1 SNV in ctDNA, combined with the ctDNA level, can predict the prognosis of patients with HCC.
format Online
Article
Text
id pubmed-7576198
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-75761982020-10-21 MLH1 single-nucleotide variant in circulating tumor DNA predicts overall survival of patients with hepatocellular carcinoma Kim, Soon Sun Eun, Jung Woo Choi, Ji-Hye Woo, Hyun Goo Cho, Hyo Jung Ahn, Hye Ri Suh, Chul Won Baek, Geum Ok Cho, Sung Won Cheong, Jae Youn Sci Rep Article Liquid biopsy can provide a strong basis for precision medicine. We aimed to identify novel single-nucleotide variants (SNVs) in circulating tumor DNA (ctDNA) in patients with hepatocellular carcinoma (HCC). Deep sequencing of plasma-derived ctDNA from 59 patients with HCC was performed using a panel of 2924 SNVs in 69 genes. In 55.9% of the patients, at least one somatic mutation was detected. Among 25 SNVs in 12 genes, four frequently observed SNVs, MLH1 (13%), STK11 (13%), PTEN (9%), and CTNNB1 (4%), were validated using droplet digital polymerase chain reaction with ctDNA from 62 patients with HCC. Three candidate SNVs were detected in 35.5% of the patients, with a frequency of 19% for MLH1 chr3:37025749T>A, 11% for STK11 chr19:1223126C>G, and 8% for PTEN chr10:87864461C>G. The MLH1 and STK11 SNVs were also confirmed in HCC tissues. The presence of the MLH1 SNV, in combination with an increased ctDNA level, predicted poor overall survival among 107 patients. MLH1 chr3:37025749T>A SNV detection in ctDNA is feasible, and thus, ctDNA can be used to detect somatic mutations in HCC. Furthermore, the presence or absence of the MLH1 SNV in ctDNA, combined with the ctDNA level, can predict the prognosis of patients with HCC. Nature Publishing Group UK 2020-10-20 /pmc/articles/PMC7576198/ /pubmed/33082400 http://dx.doi.org/10.1038/s41598-020-74494-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kim, Soon Sun
Eun, Jung Woo
Choi, Ji-Hye
Woo, Hyun Goo
Cho, Hyo Jung
Ahn, Hye Ri
Suh, Chul Won
Baek, Geum Ok
Cho, Sung Won
Cheong, Jae Youn
MLH1 single-nucleotide variant in circulating tumor DNA predicts overall survival of patients with hepatocellular carcinoma
title MLH1 single-nucleotide variant in circulating tumor DNA predicts overall survival of patients with hepatocellular carcinoma
title_full MLH1 single-nucleotide variant in circulating tumor DNA predicts overall survival of patients with hepatocellular carcinoma
title_fullStr MLH1 single-nucleotide variant in circulating tumor DNA predicts overall survival of patients with hepatocellular carcinoma
title_full_unstemmed MLH1 single-nucleotide variant in circulating tumor DNA predicts overall survival of patients with hepatocellular carcinoma
title_short MLH1 single-nucleotide variant in circulating tumor DNA predicts overall survival of patients with hepatocellular carcinoma
title_sort mlh1 single-nucleotide variant in circulating tumor dna predicts overall survival of patients with hepatocellular carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576198/
https://www.ncbi.nlm.nih.gov/pubmed/33082400
http://dx.doi.org/10.1038/s41598-020-74494-y
work_keys_str_mv AT kimsoonsun mlh1singlenucleotidevariantincirculatingtumordnapredictsoverallsurvivalofpatientswithhepatocellularcarcinoma
AT eunjungwoo mlh1singlenucleotidevariantincirculatingtumordnapredictsoverallsurvivalofpatientswithhepatocellularcarcinoma
AT choijihye mlh1singlenucleotidevariantincirculatingtumordnapredictsoverallsurvivalofpatientswithhepatocellularcarcinoma
AT woohyungoo mlh1singlenucleotidevariantincirculatingtumordnapredictsoverallsurvivalofpatientswithhepatocellularcarcinoma
AT chohyojung mlh1singlenucleotidevariantincirculatingtumordnapredictsoverallsurvivalofpatientswithhepatocellularcarcinoma
AT ahnhyeri mlh1singlenucleotidevariantincirculatingtumordnapredictsoverallsurvivalofpatientswithhepatocellularcarcinoma
AT suhchulwon mlh1singlenucleotidevariantincirculatingtumordnapredictsoverallsurvivalofpatientswithhepatocellularcarcinoma
AT baekgeumok mlh1singlenucleotidevariantincirculatingtumordnapredictsoverallsurvivalofpatientswithhepatocellularcarcinoma
AT chosungwon mlh1singlenucleotidevariantincirculatingtumordnapredictsoverallsurvivalofpatientswithhepatocellularcarcinoma
AT cheongjaeyoun mlh1singlenucleotidevariantincirculatingtumordnapredictsoverallsurvivalofpatientswithhepatocellularcarcinoma