Linked Life Data

20563638

Source:http://linkedlifedata.com/resource/pubmed/id/20563638

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-10-18
pubmed:abstractText
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?, 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1573-7217
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
124
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
555-65
pubmed:meshHeading
pubmed-meshheading:20563638-Adolescent, pubmed-meshheading:20563638-Adult, pubmed-meshheading:20563638-Aged, pubmed-meshheading:20563638-Australia, pubmed-meshheading:20563638-Breast Neoplasms, pubmed-meshheading:20563638-Chi-Square Distribution, pubmed-meshheading:20563638-DNA Methylation, pubmed-meshheading:20563638-Female, pubmed-meshheading:20563638-Fibroadenoma, pubmed-meshheading:20563638-Gene Expression Profiling, pubmed-meshheading:20563638-Genetic Markers, pubmed-meshheading:20563638-Humans, pubmed-meshheading:20563638-Logistic Models, pubmed-meshheading:20563638-Middle Aged, pubmed-meshheading:20563638-Nuclear Proteins, pubmed-meshheading:20563638-Phyllodes Tumor, pubmed-meshheading:20563638-Promoter Regions, Genetic, pubmed-meshheading:20563638-Risk Assessment, pubmed-meshheading:20563638-Risk Factors, pubmed-meshheading:20563638-Tumor Markers, Biological, pubmed-meshheading:20563638-Tumor Suppressor Proteins, pubmed-meshheading:20563638-Twist Transcription Factor, pubmed-meshheading:20563638-Young Adult
pubmed:year
2010
pubmed:articleTitle
DNA methylation profiling of phyllodes and fibroadenoma tumours of the breast.
pubmed:affiliation
Molecular Pathology Research and Development Laboratory, Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, 3002, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't