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Clonal relatedness in tumour pairs of breast cancer patients.

Artikel i vetenskaplig tidskrift
Författare Jana Biermann
Toshima Z Parris
Szilard Nemes
Anna Danielsson
Hanna Engqvist
Elisabeth Werner Rönnerman
Eva Forssell-Aronsson
Anikó Kovács
Per Karlsson
Khalil Helou
Publicerad i Breast cancer research : BCR
Volym 20
Nummer/häfte 1
ISSN 1465-542X
Publiceringsår 2018
Publicerad vid Institutionen för kliniska vetenskaper, Avdelningen för radiofysik
Institutionen för kliniska vetenskaper, Avdelningen för onkologi
Sahlgrenska Cancer Center
Språk en
Länkar dx.doi.org/10.1186/s13058-018-1022-...
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämnesord Bilateral breast cancer; Intertumour heterogeneity; Ipsilateral breast cancer; Multiple breast cancer; Similarity index; Tumour clonality
Ämneskategorier Klinisk medicin, Biologiska vetenskaper, Hälsovetenskaper

Sammanfattning

Molecular classification of tumour clonality is currently not evaluated in multiple invasive breast carcinomas, despite evidence suggesting common clonal origins. There is no consensus about which type of data (e.g. copy number, mutation, histology) and especially which statistical method is most suitable to distinguish clonal recurrences from independent primary tumours.Thirty-seven invasive breast tumour pairs were stratified according to laterality and time interval between the diagnoses of the two tumours. In a multi-omics approach, tumour clonality was analysed by integrating clinical characteristics (n = 37), DNA copy number (n = 37), DNA methylation (n = 8), gene expression microarray (n = 7), RNA sequencing (n = 3), and SNP genotyping data (n = 3). Different statistical methods, e.g. the diagnostic similarity index (SI), were used to classify the tumours as clonally related recurrences or independent primary tumours.The SI and hierarchical clustering showed similar tendencies and the highest concordance with the other methods. Concordant evidence for tumour clonality was found in 46% (17/37) of patients. Notably, no association was found between the current clinical guidelines and molecular tumour features.A more accurate classification of clonal relatedness between multiple breast tumours may help to mitigate treatment failure and relapse by integrating tumour-associated molecular features, clinical parameters, and statistical methods. Guidelines need to be defined with exact thresholds to standardise clonality testing in a routine diagnostic setting.

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