Detection of LINE-1 Hypomethylation in CfDNA of Esophageal Adenocarcinoma Patients

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2020 Feb 28

PMID 32102481

Citations 11

Authors

Elisa Boldrin

Matteo Curtarello

Marco Dallan

Rita Alfieri

Stefano Realdon

Matteo Fassan

Daniela Saggioro

Affiliations

Soon will be listed here.

Abstract

DNA methylation plays an important role in cancer development. Cancer cells exhibit two types of DNA methylation alteration: site-specific hypermethylation at promoter of oncosuppressor genes and global DNA hypomethylation. This study evaluated the methylation patterns of long interspersed nuclear element (LINE-1) sequences which, due to their relative abundance in the genome, are considered a good surrogate indicator of global DNA methylation. LINE-1 methylation status was investigated in the cell-free DNA (cfDNA) of 21 patients, 19 with esophageal adenocarcinoma (EADC) and 2 with Barrett's esophagus (BE). The two BE patients and one EADC patient were also analyzed longitudinally. Methylation status was analyzed using restriction enzymes and DNA amplification. This methodology was chosen to avoid bisulfite conversion, which we considered inadequate for cfDNA analysis. Indeed, cfDNA is characterized by poor quality and low concentration, and bisulfite conversion might worsen these conditions. Results showed that hypomethylated LINE-1 sequences are present in EADC cfDNA. Furthermore, longitudinal studies in BE suggested a correlation between methylation status of LINE-1 sequences in cfDNA and progression to EADC. In conclusion, our study indicated the feasibility of our methodological approach to detect hypomethylation events in cfDNA from EADC patients, and suggests LINE-1 methylation analysis as a new possible molecular assay to integrate into patient monitoring.

Citing Articles

Therapy response monitoring in blood plasma from esophageal adenocarcinoma patients using cell-free DNA methylation profiling.

Schoofs K, Ferro Dos Santos M, De Wilde J, Roelandt S, Van de Velde S, Decruyenaere P Sci Rep. 2024; 14(1):31112.

PMID: 39730941 PMC: 11681053. DOI: 10.1038/s41598-024-82325-7.

Identifying targeted cell-free DNA methylation regions in head and neck cancer via paired methylome analysis.

Li T, Patel K, Yu X, Yao S, Wang L, Chung C Res Sq. 2024; .

PMID: 39649173 PMC: 11623779. DOI: 10.21203/rs.3.rs-5124805/v1.

LINE-1 cfDNA Methylation as an Emerging Biomarker in Solid Cancers.

Gezer U, Ozgur E, Yoruker E, Polatoglou E, Holdenrieder S, Bronkhorst A Cancers (Basel). 2024; 16(22).

PMID: 39594682 PMC: 11592170. DOI: 10.3390/cancers16223725.

Abnormal activation of genomic LINE1 elements caused by DNA demethylation contributes to lncRNA CASC9 overexpression in esophageal squamous cell carcinoma.

Chen X, Li J, Guan X, Bai Y, Wang K Heliyon. 2024; 10(12):e32857.

PMID: 38975080 PMC: 11226909. DOI: 10.1016/j.heliyon.2024.e32857.

Epigenetic modifications of cfDNA in liquid biopsy for the cancer care continuum.

Wong J, Muralidhar R, Wang L, Huang C Biomed J. 2024; 48(1):100718.

PMID: 38522508 PMC: 11745953. DOI: 10.1016/j.bj.2024.100718.

References

Kitkumthorn N, Mutirangura A . Long interspersed nuclear element-1 hypomethylation in cancer: biology and clinical applications. Clin Epigenetics. 2012; 2(2):315-30. PMC: 3365388. DOI: 10.1007/s13148-011-0032-8. View

Agarwal A, Polineni R, Hussein Z, Vigoda I, Bhagat T, Bhattacharyya S . Role of epigenetic alterations in the pathogenesis of Barrett's esophagus and esophageal adenocarcinoma. Int J Clin Exp Pathol. 2012; 5(5):382-96. PMC: 3396065. View

Kerachian M, Kerachian M . Long interspersed nucleotide element-1 (LINE-1) methylation in colorectal cancer. Clin Chim Acta. 2018; 488:209-214. DOI: 10.1016/j.cca.2018.11.018. View

Lee K, Shin T, Kim W, Cho J . Methylation of LINE-1 in cell-free DNA serves as a liquid biopsy biomarker for human breast cancers and dog mammary tumors. Sci Rep. 2019; 9(1):175. PMC: 6336845. DOI: 10.1038/s41598-018-36470-5. View

Brock M, Gou M, Akiyama Y, Muller A, Wu T, Montgomery E . Prognostic importance of promoter hypermethylation of multiple genes in esophageal adenocarcinoma. Clin Cancer Res. 2003; 9(8):2912-9. View

Boldrin E, Rumiato E, Fassan M, Balsamo L, Realdon S, Battaglia G . Liquid biopsy as a novel tool to monitor the carcinogenesis of Barrett's esophagus. Transl Res. 2016; 176:127-31. DOI: 10.1016/j.trsl.2016.05.001. View

Edgren G, Adami H, Weiderpass E, Weiderpass Vainio E, Nyren O . A global assessment of the oesophageal adenocarcinoma epidemic. Gut. 2012; 62(10):1406-14. DOI: 10.1136/gutjnl-2012-302412. View

Ronellenfitsch U, Schwarzbach M, Hofheinz R, Kienle P, Kieser M, Slanger T . Perioperative chemo(radio)therapy versus primary surgery for resectable adenocarcinoma of the stomach, gastroesophageal junction, and lower esophagus. Cochrane Database Syst Rev. 2013; (5):CD008107. PMC: 11822331. DOI: 10.1002/14651858.CD008107.pub2. View

Zhu J, Ling Y, Xu Y, Lu M, Liu Y, Zhang C . Elevated expression of MDR1 associated with Line-1 hypomethylation in esophageal squamous cell carcinoma. Int J Clin Exp Pathol. 2016; 8(11):14392-400. PMC: 4713541. View

10.

Oakes C, La Salle S, Robaire B, Trasler J . Evaluation of a quantitative DNA methylation analysis technique using methylation-sensitive/dependent restriction enzymes and real-time PCR. Epigenetics. 2007; 1(3):146-52. DOI: 10.4161/epi.1.3.3392. View

11.

Deng J, Wang C, Xiang M, Liu F, Liu Y, Zhao K . Meta-analysis of postoperative efficacy in patients receiving chemoradiotherapy followed by surgery for resectable esophageal carcinoma. Diagn Pathol. 2014; 9:151. PMC: 4223621. DOI: 10.1186/1746-1596-9-151. View

12.

Hamilton J, Sato F, Jin Z, Greenwald B, Ito T, Mori Y . Reprimo methylation is a potential biomarker of Barrett's-Associated esophageal neoplastic progression. Clin Cancer Res. 2006; 12(22):6637-42. DOI: 10.1158/1078-0432.CCR-06-1781. View

13.

van Hagen P, Hulshof M, van Lanschot J, Steyerberg E, van Berge Henegouwen M, Wijnhoven B . Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012; 366(22):2074-84. DOI: 10.1056/NEJMoa1112088. View

14.

. Integrated genomic characterization of oesophageal carcinoma. Nature. 2017; 541(7636):169-175. PMC: 5651175. DOI: 10.1038/nature20805. View

15.

Rumiato E, Boldrin E, Malacrida S, Realdon S, Fassan M, Morbin T . Detection of genetic alterations in cfDNA as a possible strategy to monitor the neoplastic progression of Barrett's esophagus. Transl Res. 2017; 190:16-24.e1. DOI: 10.1016/j.trsl.2017.09.004. View

16.

Xiao-Jie L, Hui-Ying X, Qi X, Jiang X, Shi-Jie M . LINE-1 in cancer: multifaceted functions and potential clinical implications. Genet Med. 2015; 18(5):431-9. DOI: 10.1038/gim.2015.119. View

17.

Cordaux R, Batzer M . The impact of retrotransposons on human genome evolution. Nat Rev Genet. 2009; 10(10):691-703. PMC: 2884099. DOI: 10.1038/nrg2640. View

18.

Iwagami S, Baba Y, Watanabe M, Shigaki H, Miyake K, Ida S . Pyrosequencing assay to measure LINE-1 methylation level in esophageal squamous cell carcinoma. Ann Surg Oncol. 2011; 19(8):2726-32. DOI: 10.1245/s10434-011-2176-3. View

19.

Dubecz A, Solymosi N, Stadlhuber R, Schweigert M, Stein H, Peters J . Does the Incidence of Adenocarcinoma of the Esophagus and Gastric Cardia Continue to Rise in the Twenty-First Century?—a SEER Database Analysis. J Gastrointest Surg. 2013; 18(1):124-129. DOI: 10.1007/s11605-013-2345-8. View

20.

Fulnecek J, Kovarik A . How to interpret methylation sensitive amplified polymorphism (MSAP) profiles?. BMC Genet. 2014; 15:2. PMC: 3890580. DOI: 10.1186/1471-2156-15-2. View