TY - JOUR
T1 - Concordance of DNA methylation profiles between breast core biopsy and surgical excision specimens containing ductal carcinoma in situ (DCIS)
AU - Chen, Youdinghuan
AU - Marotti, Jonathan D.
AU - Jenson, Erik G.
AU - Onega, Tracy L.
AU - Johnson, Kevin C.
AU - Christensen, Brock C.
N1 - Funding Information:
This work was supported by the U.S. National Institute of Health (P20GM104416, R01DE022772, and 1P01CA154292), the New Hampshire Mammography Registry (U01CA086082), and the Burroughs-Wellcome Fund.
Publisher Copyright:
© 2017 The Authors
PY - 2017/8
Y1 - 2017/8
N2 - The utility and reliability of assessing molecular biomarkers for translational applications on pre-operative core biopsy specimens assume consistency of molecular profiles with larger surgical specimens. Whether DNA methylation in ductal carcinoma in situ (DCIS), measured in core biopsy and surgical specimens are similar, remains unclear. Here, we compared genome-scale DNA methylation measured in matched core biopsy and surgical specimens from DCIS, including specific DNA methylation biomarkers of subsequent invasive cancer. DNA was extracted from guided 2 mm cores of formalin fixed paraffin embedded (FFPE) specimens, bisulfite-modified, and measured on the Illumina HumanMethylation450 BeadChip. DNA methylation profiles of core biopsies exhibited high concordance with matched surgical specimens. Within-subject variability in DNA methylation was significantly lower than between-subject variability (all P < 2.20E − 16). In 641 CpGs whose methylation was related with increased hazard of invasive breast cancer, lower within-subject than between-subject variability was observed in 92.3% of the study participants (P < 0.05). Between patient-matched core biopsy and surgical specimens, < 0.6% of CpGs measured had changes in median DNA methylation > 15%, and a pathway analysis of these CpGs indicated enrichment for genes related with wound healing. Our results indicate that DNA methylation measured in core biopsies are representative of the matched surgical specimens and suggest that DCIS biomarkers measured in core biopsies can inform clinical decision-making.
AB - The utility and reliability of assessing molecular biomarkers for translational applications on pre-operative core biopsy specimens assume consistency of molecular profiles with larger surgical specimens. Whether DNA methylation in ductal carcinoma in situ (DCIS), measured in core biopsy and surgical specimens are similar, remains unclear. Here, we compared genome-scale DNA methylation measured in matched core biopsy and surgical specimens from DCIS, including specific DNA methylation biomarkers of subsequent invasive cancer. DNA was extracted from guided 2 mm cores of formalin fixed paraffin embedded (FFPE) specimens, bisulfite-modified, and measured on the Illumina HumanMethylation450 BeadChip. DNA methylation profiles of core biopsies exhibited high concordance with matched surgical specimens. Within-subject variability in DNA methylation was significantly lower than between-subject variability (all P < 2.20E − 16). In 641 CpGs whose methylation was related with increased hazard of invasive breast cancer, lower within-subject than between-subject variability was observed in 92.3% of the study participants (P < 0.05). Between patient-matched core biopsy and surgical specimens, < 0.6% of CpGs measured had changes in median DNA methylation > 15%, and a pathway analysis of these CpGs indicated enrichment for genes related with wound healing. Our results indicate that DNA methylation measured in core biopsies are representative of the matched surgical specimens and suggest that DCIS biomarkers measured in core biopsies can inform clinical decision-making.
KW - DCIS core biopsies
KW - DNA methylation
KW - Epigenetic biomarkers
KW - Illumina 450k
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U2 - 10.1016/j.yexmp.2017.07.001
DO - 10.1016/j.yexmp.2017.07.001
M3 - Article
C2 - 28711544
AN - SCOPUS:85024362691
SN - 0014-4800
VL - 103
SP - 78
EP - 83
JO - Experimental and Molecular Pathology
JF - Experimental and Molecular Pathology
IS - 1
ER -