Methylation biomarkers for pleomorphic lobular breast cancer - a short report

Cathy B.  Moelans; Eva J. Vlug; Cigdem Ercan; Peter Bult; Horst Buerger; Gabor Cserni; Paul J. van Diest; Patrick W B Derksen

doi:10.1007/s13402-015-0241-9

Methylation biomarkers for pleomorphic lobular breast cancer - a short report

Cathy B. Moelans^*, Eva J. Vlug, Cigdem Ercan, Peter Bult, Horst Buerger, Gabor Cserni, Paul J. van Diest, Patrick W B Derksen

^*Corresponding author for this work

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Abstract

Background

Pleomorphic invasive lobular cancer (pleomorphic ILC) is a rare variant of ILC that is characterized by a classic ILC-like growth pattern combined with an infiltrative ductal cancer (IDC)-like high nuclear atypicality. There is an ongoing discussion whether pleomorphic ILC is a dedifferentiated form of ILC or in origin an IDC with a secondary loss of cohesion. Since gene promoter hypermethylation is an early event in breast carcinogenesis and thus may provide information on tumor progression, we set out to compare the methylation patterns of pleomorphic ILC, classic ILC and IDC. In addition, we aimed at analyzing the methylation status of pleomorphic ILC.

Methods

We performed promoter methylation profiling of 24 established and putative tumor suppressor genes by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) analysis in 20 classical ILC, 16 pleomorphic ILC and 20 IDC cases.

Results

We found that pleomorphic ILC showed relatively low TP73 and MLH1 methylation levels and relatively high RASSF1A methylation levels compared to classic ILC. Compared to IDC, pleomorphic ILC showed relatively low MLH1 and BRCA1 methylation levels. Hierarchical cluster analysis revealed a similar methylation pattern for pleomorphic ILC and IDC, while the methylation pattern of classic ILC was different.

Conclusion

This is the first report to identify TP73, RASSF1A, MLH1 and BRCA1 as possible biomarkers to distinguish pleomorphic ILC from classic ILC and IDC.

Original language	English
Pages (from-to)	397-405
Number of pages	9
Journal	Cellular oncology
Volume	38
Issue number	5
DOIs	https://doi.org/10.1007/s13402-015-0241-9
Publication status	Published - Oct 2015

Keywords

Sporadic breast cancer
Lobular breast cancer
Pleomorphic lobular breast cancer
DNA hypermethylation
MS-MLPA
Epigenetics
PROMOTER HYPERMETHYLATION
SPORADIC BREAST
DNA METHYLATION
E-CADHERIN
MAMMARY-CARCINOMA
EXPRESSION
RASSF1A
TUMORS
BRCA1
DIFFERENTIATION

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@article{476252d1f71c412093cb508ec3b5583d,

title = "Methylation biomarkers for pleomorphic lobular breast cancer - a short report",

abstract = "Background Pleomorphic invasive lobular cancer (pleomorphic ILC) is a rare variant of ILC that is characterized by a classic ILC-like growth pattern combined with an infiltrative ductal cancer (IDC)-like high nuclear atypicality. There is an ongoing discussion whether pleomorphic ILC is a dedifferentiated form of ILC or in origin an IDC with a secondary loss of cohesion. Since gene promoter hypermethylation is an early event in breast carcinogenesis and thus may provide information on tumor progression, we set out to compare the methylation patterns of pleomorphic ILC, classic ILC and IDC. In addition, we aimed at analyzing the methylation status of pleomorphic ILC.Methods We performed promoter methylation profiling of 24 established and putative tumor suppressor genes by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) analysis in 20 classical ILC, 16 pleomorphic ILC and 20 IDC cases.Results We found that pleomorphic ILC showed relatively low TP73 and MLH1 methylation levels and relatively high RASSF1A methylation levels compared to classic ILC. Compared to IDC, pleomorphic ILC showed relatively low MLH1 and BRCA1 methylation levels. Hierarchical cluster analysis revealed a similar methylation pattern for pleomorphic ILC and IDC, while the methylation pattern of classic ILC was different.Conclusion This is the first report to identify TP73, RASSF1A, MLH1 and BRCA1 as possible biomarkers to distinguish pleomorphic ILC from classic ILC and IDC.",

keywords = "Sporadic breast cancer, Lobular breast cancer, Pleomorphic lobular breast cancer, DNA hypermethylation, MS-MLPA, Epigenetics, PROMOTER HYPERMETHYLATION, SPORADIC BREAST, DNA METHYLATION, E-CADHERIN, MAMMARY-CARCINOMA, EXPRESSION, RASSF1A, TUMORS, BRCA1, DIFFERENTIATION",

author = "Moelans, {Cathy B.} and Vlug, {Eva J.} and Cigdem Ercan and Peter Bult and Horst Buerger and Gabor Cserni and {van Diest}, {Paul J.} and Derksen, {Patrick W B}",

year = "2015",

month = oct,

doi = "10.1007/s13402-015-0241-9",

language = "English",

volume = "38",

pages = "397--405",

journal = "Cellular oncology",

issn = "2211-3428",

publisher = "Springer Netherlands",

number = "5",

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TY - JOUR

T1 - Methylation biomarkers for pleomorphic lobular breast cancer - a short report

AU - Moelans, Cathy B.

AU - Vlug, Eva J.

AU - Ercan, Cigdem

AU - Bult, Peter

AU - Buerger, Horst

AU - Cserni, Gabor

AU - van Diest, Paul J.

AU - Derksen, Patrick W B

PY - 2015/10

Y1 - 2015/10

N2 - Background Pleomorphic invasive lobular cancer (pleomorphic ILC) is a rare variant of ILC that is characterized by a classic ILC-like growth pattern combined with an infiltrative ductal cancer (IDC)-like high nuclear atypicality. There is an ongoing discussion whether pleomorphic ILC is a dedifferentiated form of ILC or in origin an IDC with a secondary loss of cohesion. Since gene promoter hypermethylation is an early event in breast carcinogenesis and thus may provide information on tumor progression, we set out to compare the methylation patterns of pleomorphic ILC, classic ILC and IDC. In addition, we aimed at analyzing the methylation status of pleomorphic ILC.Methods We performed promoter methylation profiling of 24 established and putative tumor suppressor genes by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) analysis in 20 classical ILC, 16 pleomorphic ILC and 20 IDC cases.Results We found that pleomorphic ILC showed relatively low TP73 and MLH1 methylation levels and relatively high RASSF1A methylation levels compared to classic ILC. Compared to IDC, pleomorphic ILC showed relatively low MLH1 and BRCA1 methylation levels. Hierarchical cluster analysis revealed a similar methylation pattern for pleomorphic ILC and IDC, while the methylation pattern of classic ILC was different.Conclusion This is the first report to identify TP73, RASSF1A, MLH1 and BRCA1 as possible biomarkers to distinguish pleomorphic ILC from classic ILC and IDC.

AB - Background Pleomorphic invasive lobular cancer (pleomorphic ILC) is a rare variant of ILC that is characterized by a classic ILC-like growth pattern combined with an infiltrative ductal cancer (IDC)-like high nuclear atypicality. There is an ongoing discussion whether pleomorphic ILC is a dedifferentiated form of ILC or in origin an IDC with a secondary loss of cohesion. Since gene promoter hypermethylation is an early event in breast carcinogenesis and thus may provide information on tumor progression, we set out to compare the methylation patterns of pleomorphic ILC, classic ILC and IDC. In addition, we aimed at analyzing the methylation status of pleomorphic ILC.Methods We performed promoter methylation profiling of 24 established and putative tumor suppressor genes by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) analysis in 20 classical ILC, 16 pleomorphic ILC and 20 IDC cases.Results We found that pleomorphic ILC showed relatively low TP73 and MLH1 methylation levels and relatively high RASSF1A methylation levels compared to classic ILC. Compared to IDC, pleomorphic ILC showed relatively low MLH1 and BRCA1 methylation levels. Hierarchical cluster analysis revealed a similar methylation pattern for pleomorphic ILC and IDC, while the methylation pattern of classic ILC was different.Conclusion This is the first report to identify TP73, RASSF1A, MLH1 and BRCA1 as possible biomarkers to distinguish pleomorphic ILC from classic ILC and IDC.

KW - Sporadic breast cancer

KW - Lobular breast cancer

KW - Pleomorphic lobular breast cancer

KW - DNA hypermethylation

KW - MS-MLPA

KW - Epigenetics

KW - PROMOTER HYPERMETHYLATION

KW - SPORADIC BREAST

KW - DNA METHYLATION

KW - E-CADHERIN

KW - MAMMARY-CARCINOMA

KW - EXPRESSION

KW - RASSF1A

KW - TUMORS

KW - BRCA1

KW - DIFFERENTIATION

UR - http://www.scopus.com/inward/record.url?scp=84944078419&partnerID=8YFLogxK

U2 - 10.1007/s13402-015-0241-9

DO - 10.1007/s13402-015-0241-9

M3 - Article

AN - SCOPUS:84944078419

SN - 2211-3428

VL - 38

SP - 397

EP - 405

JO - Cellular oncology

JF - Cellular oncology

IS - 5

ER -

Methylation biomarkers for pleomorphic lobular breast cancer - a short report

Abstract

Keywords

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