Assessment of DNA methylation profiling and copy number variation as indications of clonal relationship in ipsilateral and contralateral breast cancers to distinguish recurrent breast cancer from a second primary tumour

BMC Cancer

Research Article

Terence P. Speed¹  Jason Li²  Ian G. Campbell³  Elena A. Takano⁴  Stephen B. Fox⁵  Katie T. Huang⁵  Thomas Mikeska⁶  Alexander Dobrovic⁷  Ewan K A Millar⁸  Peter H. Graham⁹  Samantha E. Boyle^1,10 

[1] Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, 3052, Parkville, VIC, Australia;Bioinformatics, Peter MacCallum Cancer Centre, St. Andrew’s Place, 3002, East Melbourne, VIC, Australia;Department of Pathology and Sir Peter MacCallum Department of Oncology, University of Melbourne, Grattan Street, 3010, Parkville, VIC, Australia;VBCRC Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, St. Andrew’s Place, 3002, East Melbourne, VIC, Australia;Molecular Pathology Research and Development Laboratory, Department of Pathology, Peter MacCallum Cancer Centre, St. Andrew’s Place, 3002, East Melbourne, VIC, Australia;Molecular Pathology Research and Development Laboratory, Department of Pathology, Peter MacCallum Cancer Centre, St. Andrew’s Place, 3002, East Melbourne, VIC, Australia;Department of Pathology and Sir Peter MacCallum Department of Oncology, University of Melbourne, Grattan Street, 3010, Parkville, VIC, Australia;Molecular Pathology Research and Development Laboratory, Department of Pathology, Peter MacCallum Cancer Centre, St. Andrew’s Place, 3002, East Melbourne, VIC, Australia;Department of Pathology and Sir Peter MacCallum Department of Oncology, University of Melbourne, Grattan Street, 3010, Parkville, VIC, Australia;Translational Genomics and Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute, Studley Road, 3084, Heidelberg, VIC, Australia;Molecular Pathology Research and Development Laboratory, Department of Pathology, Peter MacCallum Cancer Centre, St. Andrew’s Place, 3002, East Melbourne, VIC, Australia;Department of Pathology and Sir Peter MacCallum Department of Oncology, University of Melbourne, Grattan Street, 3010, Parkville, VIC, Australia;Translational Genomics and Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute, Studley Road, 3084, Heidelberg, VIC, Australia;School of Cancer Medicine, La Trobe University, 3084, Bundoora, VIC, Australia;South Eastern Area Laboratory Service (SEALS), St. George Hospital, Gary Street, 2217, Kogarah, NSW, Australia;The Kinghorn Cancer Centre & Garvan Institute of Medical Research, 384 Victoria Street, 2010, Darlinghurst, NSW, Australia;School of Medicine and Health Sciences, University of Western Sydney, Narellan Road, 2560, Campbelltown, NSW, Australia;Faculty of Medicine, University of NSW, High Street, 2052, Kensington, NSW, Australia;The Kinghorn Cancer Centre & Garvan Institute of Medical Research, 384 Victoria Street, 2010, Darlinghurst, NSW, Australia;School of Medicine and Health Sciences, University of Western Sydney, Narellan Road, 2560, Campbelltown, NSW, Australia;VBCRC Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, St. Andrew’s Place, 3002, East Melbourne, VIC, Australia;

关键词: DNA methylation;    Comparative genomic hybridisation;    Ipsilateral;    Contralateral;    Breast;   

DOI  :  10.1186/s12885-015-1676-0

 received in 2014-12-12, accepted in 2015-10-01,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundPatients with breast cancer have an increased risk of developing subsequent breast cancers. It is important to distinguish whether these tumours are de novo or recurrences of the primary tumour in order to guide the appropriate therapy. Our aim was to investigate the use of DNA methylation profiling and array comparative genomic hybridization (aCGH) to determine whether the second tumour is clonally related to the first tumour.MethodsMethylation-sensitive high-resolution melting was used to screen promoter methylation in a panel of 13 genes reported as methylated in breast cancer (RASSF1A, TWIST1, APC, WIF1, MGMT, MAL, CDH13, RARβ, BRCA1, CDH1, CDKN2A, TP73, and GSTP1) in 29 tumour pairs (16 ipsilateral and 13 contralateral). Using the methylation profile of these genes, we employed a Bayesian and an empirical statistical approach to estimate clonal relationship. Copy number alterations were analysed using aCGH on the same set of tumour pairs.ResultsThere is a higher probability of the second tumour being recurrent in ipsilateral tumours compared with contralateral tumours (38 % versus 8 %; p <0.05) based on the methylation profile. Using previously reported recurrence rates as Bayesian prior probabilities, we classified 69 % of ipsilateral and 15 % of contralateral tumours as recurrent. The inferred clonal relationship results of the tumour pairs were generally concordant between methylation profiling and aCGH.ConclusionOur results show that DNA methylation profiling as well as aCGH have potential as diagnostic tools in improving the clinical decisions to differentiate recurrences from a second de novo tumour.

【 授权许可】

CC BY   
© Huang et al. 2015

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