title: Inter- and intra-tumoral heterogeneity in DNA damage evaluated by comet assay in early breast cancer patients.
abstract: 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.
authors.affiliation: Translational Research Unit, Department of Oncology, Hospital of Prato, Istituto Toscano Tumori, Prato, Italy. fgalardi@usl4.toscana.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Galardi
authors.forename: Catherine
authors.initials: C
authors.lastname: Oakman
authors.forename: Maria Caterina
authors.initials: MC
authors.lastname: Truglia
authors.forename: Silvia
authors.initials: S
authors.lastname: Cappadona
authors.forename: Annibale
authors.initials: A
authors.lastname: Biggeri
authors.forename: Laura
authors.initials: L
authors.lastname: Grisotto
authors.forename: Lisa
authors.initials: L
authors.lastname: Giovannelli
authors.forename: Silvia
authors.initials: S
authors.lastname: Bessi
authors.forename: Augusto
authors.initials: A
authors.lastname: Giannini
authors.forename: Laura
authors.initials: L
authors.lastname: Biganzoli
authors.forename: Libero
authors.initials: L
authors.lastname: Santarpia
authors.forename: Angelo
authors.initials: A
authors.lastname: Di Leo
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D020552:Comet Assay / Q000379:methods*; D020732:Cytogenetic Analysis / Q000379:methods*; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D007558:Italy; D015162:Micronucleus Tests; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects
chemical_list: D004273:DNA, Neoplasm