title: Frequent genetic differences between matched primary and metastatic breast cancer provide an approach to identification of biomarkers for disease progression.
abstract: Breast cancer is a major cause of morbidity and mortality in women and its metastatic spread is the principal reason behind the fatal outcome. Metastasis-related research of breast cancer is however underdeveloped when compared with the abundant literature on primary tumors. We applied an unexplored approach comparing at high resolution the genomic profiles of primary tumors and synchronous axillary lymph node metastases from 13 patients with breast cancer. Overall, primary tumors displayed 20% higher number of aberrations than metastases. In all but two patients, we detected in total 157 statistically significant differences between primary lesions and matched metastases. We further observed differences that can be linked to metastatic disease and there was also an overlapping pattern of changes between different patients. Many of the differences described here have been previously linked to poor patient survival, suggesting that this is a viable approach toward finding biomarkers for disease progression and definition of new targets useful for development of anticancer drugs. Frequent genetic differences between primary tumors and metastases in breast cancer also question, at least to some extent, the role of primary tumors as a surrogate subject of study for the systemic disease.
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Andrzej B
authors.initials: AB
authors.lastname: Popławski
authors.forename: Michał
authors.initials: M
authors.lastname: Jankowski
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Erickson
authors.forename: Teresita
authors.initials: T
authors.lastname: Díaz de Ståhl
authors.forename: E Christopher
authors.initials: EC
authors.lastname: Partridge
authors.forename: Chiquito
authors.initials: C
authors.lastname: Crasto
authors.forename: Jingyu
authors.initials: J
authors.lastname: Guo
authors.forename: John
authors.initials: J
authors.lastname: Gibson
authors.forename: Uwe
authors.initials: U
authors.lastname: Menzel
authors.forename: Carl Eg
authors.initials: CE
authors.lastname: Bruder
authors.forename: Aneta
authors.initials: A
authors.lastname: Kaczmarczyk
authors.forename: Magdalena
authors.initials: M
authors.lastname: Benetkiewicz
authors.forename: Robin
authors.initials: R
authors.lastname: Andersson
authors.forename: Johanna
authors.initials: J
authors.lastname: Sandgren
authors.forename: Barbara
authors.initials: B
authors.lastname: Zegarska
authors.forename: Dariusz
authors.initials: D
authors.lastname: Bała
authors.forename: Ewa
authors.initials: E
authors.lastname: Srutek
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Piotrowski
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zegarski
authors.forename: Jan P
authors.initials: JP
authors.lastname: Dumanski
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D014408:Biomarkers, Tumor