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Clin Epigenetics. 2017 May 2;9:46. doi: 10.1186/s13148-017-0347-1. eCollection 2017.

The CpG island methylator phenotype is concordant between primary colorectal carcinoma and matched distant metastases.

Cohen SA#1,2,3, Yu M#1,4, Baker K5,6, Redman M5,6, Wu C1,7,4, Heinzerling TJ1,4, Wirtz RM8,9, Charalambous E10,11, Pentheroudakis G12,13, Kotoula V10,14,11, Kalogeras KT10,15,16, Fountzilas G10,17,18, Grady WM1,19,4.

Author information

1
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 USA.
2
Division of Oncology, University of Washington, Seattle, WA USA.
3
825 Eastlake Ave E, G4-830, Seattle, WA 98109 USA.
4
1100 Fairview Ave N, D4-100, Seattle, WA 98109 USA.
5
Clinical Statistics, Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA USA.
6
1100 Fairview Ave N, M2-B230, Seattle, WA 98109 USA.
7
College of Life Sciences, Hebei University, Baoding, Hebei People's Republic of China.
8
STRATIFYER Molecular Pathology GmbH, Cologne, Germany.
9
Werthmann Str. Str. 1c, D-50935 Cologne, Germany.
10
Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece.
11
University Campus, Building 17B, 540 06 Thessaloniki, Greece.
12
Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece.
13
Niarchos Av, Ioannina, 455 00 Greece.
14
Department of Pathology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
15
Translational Research Section, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece.
16
18 Hatzikonstanti Str, 115 24 Athens, Greece.
17
Aristotle University of Thessaloniki, Thessaloniki, Greece.
18
30 Kapetan Kotta Str, 552 36 Panorama, Thessaloniki Greece.
19
Division of Gastroenterology, University of Washington School of Medicine, Seattle, WA USA.
#
Contributed equally

Abstract

BACKGROUND:

The CpG island methylator phenotype (CIMP) in stage III colon cancer (CRC) has been associated with improved survival after treatment with adjuvant irinotecan-based chemotherapy. In this analysis, we determine whether CIMP status in the primary CRC is concordant with the CIMP status of matched metastases in order to determine if assessment of CIMP status in the primary tumor can be used to predict CIMP status of metastatic disease, which is relevant for patient management as well as for understanding the biology of CIMP CRCs.

METHODS:

We assessed the CIMP status of 70 pairs of primary CRC and matched metastases using a CRC-specific panel of five markers (CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1) where CIMP positive was defined as 3/5 positive markers at a percent methylated reference threshold of ≥10%. Concordance was compared using the Fisher's exact test and P < 0.05 was considered significant.

RESULTS:

Sixty-nine of the pairs (98.6%) showed concordant CIMP status in the primary tumor and matched metastasis; five (7.0%) of the pairs were concordantly CIMP positive. Only one pair (1.4%) had divergent CIMP status, demonstrating CIMP positivity (4/5 markers positive) in the primary tumor, while the matched metastasis was CIMP negative (0 markers positive).

CONCLUSIONS:

CIMP status is generally concordant between primary CRCs and matched metastases. Thus, CIMP status in the primary tumor is maintained in matched metastases and can be used to inform CIMP-based therapy options for the metastases.

KEYWORDS:

Biomarker; CIMP; Colorectal cancer; DNA methylation; Metastatic

PMID:
28469732
PMCID:
PMC5414304
DOI:
10.1186/s13148-017-0347-1
[Indexed for MEDLINE]
Free PMC Article

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