Novel methylated DNA markers accurately discriminate Lynch syndrome associated colorectal neoplasia

Veroushka Ballester; William R. Taylor; Seth W. Slettedahl; Douglas W. Mahoney; Tracy C. Yab; Frank A. Sinicrope; Clement R. Boland; Graham P. Lidgard; Marcia R. Cruz-Correa; Thomas C. Smyrk; Lisa A. Boardman; David A. Ahlquist; John B. Kisiel

doi:10.2217/epi-2020-0132

Novel methylated DNA markers accurately discriminate Lynch syndrome associated colorectal neoplasia

Veroushka Ballester, William R. Taylor, Seth W. Slettedahl, Douglas W. Mahoney, Tracy C. Yab, Frank A. Sinicrope, Clement R. Boland, Graham P. Lidgard, Marcia R. Cruz-Correa, Thomas C. Smyrk, Lisa A. Boardman, David A. Ahlquist, John B. Kisiel

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Aim: Acquired molecular changes in Lynch syndrome (LS) colorectal tumors have been largely unstudied. We identified methylated DNA markers (MDMs) for discrimination of colorectal neoplasia in LS and determined if these MDMs were comparably discriminant in sporadic patients. Patients & methods: For LS discovery, we evaluated DNA from 53 colorectal case and control tissues using next generation sequencing. For validation, blinded methylation-specific PCR assays to the selected MDMs were performed on 197 cases and controls. Results: OPLAH was the most discriminant MDM with areas under the receiver operating characteristic curve ≥0.97 for colorectal neoplasia in LS and sporadic tissues. ALKBH5, was uniquely hypermethylated in LS neoplasms. Conclusion: Highly discriminant MDMs for colorectal neoplasia in LS were identified with potential use in screening and surveillance.

Original language	English (US)
Pages (from-to)	2173-2187
Number of pages	15
Journal	Epigenomics
Volume	12
Issue number	24
DOIs	https://doi.org/10.2217/epi-2020-0132
State	Published - Dec 2020

Keywords

DNA methylation
biomarkers
colorectal neoplasms
colorectal neoplasms
colorectal physiology
colorectal prevention and control
hereditary nonpolyposis

ASJC Scopus subject areas

Genetics
Cancer Research

Access to Document

10.2217/epi-2020-0132

Cite this

Ballester, V., Taylor, W. R., Slettedahl, S. W., Mahoney, D. W., Yab, T. C., Sinicrope, F. A., Boland, C. R., Lidgard, G. P., Cruz-Correa, M. R., Smyrk, T. C., Boardman, L. A., Ahlquist, D. A., & Kisiel, J. B. (2020). Novel methylated DNA markers accurately discriminate Lynch syndrome associated colorectal neoplasia. Epigenomics, 12(24), 2173-2187. https://doi.org/10.2217/epi-2020-0132

@article{62c38738c6c84d07ad911fc5f9c7d74b,

title = "Novel methylated DNA markers accurately discriminate Lynch syndrome associated colorectal neoplasia",

abstract = "Aim: Acquired molecular changes in Lynch syndrome (LS) colorectal tumors have been largely unstudied. We identified methylated DNA markers (MDMs) for discrimination of colorectal neoplasia in LS and determined if these MDMs were comparably discriminant in sporadic patients. Patients & methods: For LS discovery, we evaluated DNA from 53 colorectal case and control tissues using next generation sequencing. For validation, blinded methylation-specific PCR assays to the selected MDMs were performed on 197 cases and controls. Results: OPLAH was the most discriminant MDM with areas under the receiver operating characteristic curve ≥0.97 for colorectal neoplasia in LS and sporadic tissues. ALKBH5, was uniquely hypermethylated in LS neoplasms. Conclusion: Highly discriminant MDMs for colorectal neoplasia in LS were identified with potential use in screening and surveillance.",

keywords = "DNA methylation, biomarkers, colorectal neoplasms, colorectal neoplasms, colorectal physiology, colorectal prevention and control, hereditary nonpolyposis",

author = "Veroushka Ballester and Taylor, {William R.} and Slettedahl, {Seth W.} and Mahoney, {Douglas W.} and Yab, {Tracy C.} and Sinicrope, {Frank A.} and Boland, {Clement R.} and Lidgard, {Graham P.} and Cruz-Correa, {Marcia R.} and Smyrk, {Thomas C.} and Boardman, {Lisa A.} and Ahlquist, {David A.} and Kisiel, {John B.}",

year = "2020",

month = dec,

doi = "10.2217/epi-2020-0132",

language = "English (US)",

volume = "12",

pages = "2173--2187",

journal = "Epigenomics",

issn = "1750-1911",

publisher = "Future Medicine Ltd.",

number = "24",

}

TY - JOUR

T1 - Novel methylated DNA markers accurately discriminate Lynch syndrome associated colorectal neoplasia

AU - Ballester, Veroushka

AU - Taylor, William R.

AU - Slettedahl, Seth W.

AU - Mahoney, Douglas W.

AU - Yab, Tracy C.

AU - Sinicrope, Frank A.

AU - Boland, Clement R.

AU - Lidgard, Graham P.

AU - Cruz-Correa, Marcia R.

AU - Smyrk, Thomas C.

AU - Boardman, Lisa A.

AU - Ahlquist, David A.

AU - Kisiel, John B.

PY - 2020/12

Y1 - 2020/12

N2 - Aim: Acquired molecular changes in Lynch syndrome (LS) colorectal tumors have been largely unstudied. We identified methylated DNA markers (MDMs) for discrimination of colorectal neoplasia in LS and determined if these MDMs were comparably discriminant in sporadic patients. Patients & methods: For LS discovery, we evaluated DNA from 53 colorectal case and control tissues using next generation sequencing. For validation, blinded methylation-specific PCR assays to the selected MDMs were performed on 197 cases and controls. Results: OPLAH was the most discriminant MDM with areas under the receiver operating characteristic curve ≥0.97 for colorectal neoplasia in LS and sporadic tissues. ALKBH5, was uniquely hypermethylated in LS neoplasms. Conclusion: Highly discriminant MDMs for colorectal neoplasia in LS were identified with potential use in screening and surveillance.

AB - Aim: Acquired molecular changes in Lynch syndrome (LS) colorectal tumors have been largely unstudied. We identified methylated DNA markers (MDMs) for discrimination of colorectal neoplasia in LS and determined if these MDMs were comparably discriminant in sporadic patients. Patients & methods: For LS discovery, we evaluated DNA from 53 colorectal case and control tissues using next generation sequencing. For validation, blinded methylation-specific PCR assays to the selected MDMs were performed on 197 cases and controls. Results: OPLAH was the most discriminant MDM with areas under the receiver operating characteristic curve ≥0.97 for colorectal neoplasia in LS and sporadic tissues. ALKBH5, was uniquely hypermethylated in LS neoplasms. Conclusion: Highly discriminant MDMs for colorectal neoplasia in LS were identified with potential use in screening and surveillance.

KW - DNA methylation

KW - biomarkers

KW - colorectal neoplasms

KW - colorectal physiology

KW - colorectal prevention and control

KW - hereditary nonpolyposis

UR - http://www.scopus.com/inward/record.url?scp=85099262575&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85099262575&partnerID=8YFLogxK

U2 - 10.2217/epi-2020-0132

DO - 10.2217/epi-2020-0132

M3 - Article

C2 - 33350853

AN - SCOPUS:85099262575

SN - 1750-1911

VL - 12

SP - 2173

EP - 2187

JO - Epigenomics

JF - Epigenomics

IS - 24

ER -

Novel methylated DNA markers accurately discriminate Lynch syndrome associated colorectal neoplasia

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this