Inter- and intra-tumoral heterogeneity in DNA damage evaluated by comet assay in early breast cancer patients

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• 作者：Francesca Galardi^a ; ^f ; ^{fgalardi@usl4.toscana.it} ; Catherine Oakman^b ; ^f ; ^{coakman@usl4.toscana.it} ; Maria Caterina Truglia^c ; ^{mtruglia@usl4.toscana.it} ; Silvia Cappadona^b ; ^{scappadona@usl4.toscana.it} ; Annibale Biggeri^d ; ^{abiggeri@ds.unifi.it} ; Laura Grisotto^d ; ^{grisotto@ds.unifi.it} ; Lisa Giovannelli^e ; ^{lisa.giovannelli@unifi.it} ; Silvia Bessi^a ; ^{sbessi@usl4.toscana.it} ; Augusto Giannini^c ; ^{agiannini@usl4.toscana.it} ; Laura Biganzoli^b ; ^{lbiganzoli@usl4.toscana.it} ; Libero Santarpia^a ; ^{lsantarpia@usl4.toscana.it} ; Angelo Di Leo^b ; ^{adileo@usl4.toscana.it}
• 关键词：Breast cancer ; Comet assay ; DNA damage ; Single cell gel electrophoresis
• 刊名：The Breast
• 出版年：2012
• 期刊代码：321_09609776
• 类别：med
• 出版时间：June, 2012
• 卷：21
• 期：3
• 页码：336-342
• 文件大小：559 K

摘要

There are no clinical tools to functionally assess degree of DNA damage in breast cancer. The comet assay is an accepted research tool for assessing DNA damage, however, most cancer studies have assessed lymphocytes as surrogate cells. The aim of this pilot study was to use the comet assay in early breast cancer directly in tumor tissue to compare DNA damage between and within traditionally defined subgroups, and to explore intra-tumoral heterogeneity. Scrapings of tumor and healthy breast tissue were obtained at primary surgery from 104 women. Comet assay was applied to quantitatively assess DNA damage, revealing substantial inter- and intra-subgroup variation. Marked intra-tumoral heterogeneity was evident across all subgroups. The degree of DNA damage for an individual could not be predicted by breast cancer subgroup. Comet assay warrants further study as a potential clinical tool for identification of tumoral DNA damage and ultimately, individualised use of DNA damaging therapy.