DNA methylation profiling of phyllodes and fibroadenoma tumours of the breast

Huang, Katie T., Dobrovic, Alexander, Yan, Max, Karim, Rooshdiya Z., Lee, C. Soon, Lakhani, Sunil R. and Fox, Stephen B. (2010) DNA methylation profiling of phyllodes and fibroadenoma tumours of the breast. Breast Cancer Research and Treatment, 124 2: 555-565. doi:10.1007/s10549-010-0970-4

Author Huang, Katie T.
Dobrovic, Alexander
Yan, Max
Karim, Rooshdiya Z.
Lee, C. Soon
Lakhani, Sunil R.
Fox, Stephen B.
Title DNA methylation profiling of phyllodes and fibroadenoma tumours of the breast
Journal name Breast Cancer Research and Treatment   Check publisher's open access policy
ISSN 0167-6806
Publication date 2010-11
Sub-type Article (original research)
DOI 10.1007/s10549-010-0970-4
Volume 124
Issue 2
Start page 555
End page 565
Total pages 11
Place of publication Dordrecht, Germany
Publisher Springer
Collection year 2011
Language eng
Formatted abstract
Phyllodes tumours and cellular fibroadenomas are both fibroepithelial tumours of the breast. Phyllodes tumours, unlike fibroadenomas, have the ability to recur and metastasise. Although these lesions can be distinguished by their stromal cellularity, mitotic index, presence or absence of stromal overgrowth and cellular atypia, there is overlap and not infrequently a definitive diagnosis cannot be made, particularly on biopsy. We sought to evaluate whether DNA promoter methylation profiling using selected genes known to be methylated in cancer would allow us to learn more about the biology of these tumours, and whether it could identify methylation markers that could differentiate phyllodes tumours from fibroadenomas and/or distinguish phyllodes tumours of different grades. Methylation-sensitive high resolution melting (MS-HRM) was used to screen promoter DNA methylation changes in 86 phyllodes tumours (15 benign, 28 borderline, 43 malignant) and 26 fibroadenomas. A panel of 11 genes (RASSF1A, TWIST1, APC, WIF1, MGMT, MAL, RAR beta, CDKN2A, CDH1, TP73 and MLH1) was tested. Methylation status was correlated with histology and with clinicopathological parameters. Five of the gene promoters showed some methylation in a proportion of phyllodes tumours; RASSF1A, 45.3%; TWIST1, 10.7%; APC, 4.1%; WIF1, 2.9% and MGMT, 1.3%. Only two genes showed any methylation in fibroadenomas usually at background levels; RASSF1A, 53.8% and MGMT, 8.3%. No CDKN2A methylation was observed in either tumour type, contrary to previous reports. Overall, the methylation patterns differed little from that which might be seen in normal cells. However, significant levels of methylation of RASSF1A (24.4%) and TWIST1 (7.1%) was observed in some phyllodes tumours. Elevated RASSF1A and/or TWIST1 methylation was significantly associated with phyllodes tumours compared with fibroadenomas (P = 0.02), TWIST1 methylation correlated with increasing malignancy in phyllodes tumours (P < 0.001). In conclusion, assessment of methylation of RASSF1A and TWIST1 may aid in the diagnosis of phyllodes tumours. The absence of frequent methylation in fibroadenomas supports a non-neoplastic origin.
© Springer Science+Business Media, LLC. 2010

Keyword Phyllodes breast
DNA methylation
Soft-tisseu sarcomas
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2011 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 22 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 26 times in Scopus Article | Citations
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Created: Sun, 07 Nov 2010, 00:15:28 EST