title: Catalog of genetic progression of human cancers: breast cancer.
abstract: With the rapid development of next-generation sequencing, deeper insights are being gained into the molecular evolution that underlies the development and clinical progression of breast cancer. It is apparent that during evolution, breast cancers acquire thousands of mutations including single base pair substitutions, insertions, deletions, copy number aberrations, and structural rearrangements. As a consequence, at the whole genome level, no two cancers are identical and few cancers even share the same complement of "driver" mutations. Indeed, two samples from the same cancer may also exhibit extensive differences due to constant remodeling of the genome over time. In this review, we summarize recent studies that extend our understanding of the genomic basis of cancer progression. Key biological insights include the following: subclonal diversification begins early in cancer evolution, being detectable even in in situ lesions; geographical stratification of subclonal structure is frequent in primary tumors and can include therapeutically targetable alterations; multiple distant metastases typically arise from a common metastatic ancestor following a "metastatic cascade" model; systemic therapy can unmask preexisting resistant subclones or influence further treatment sensitivity and disease progression. We conclude the review by describing novel approaches such as the analysis of circulating DNA and patient-derived xenografts that promise to further our understanding of the genomic changes occurring during cancer evolution and guide treatment decision making.
authors.affiliation: J.-C. Heuson Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Boulevard de Waterloo 121, 1000, Brussels, Belgium. christine.desmedt@bordet.be.
authors.forename: Christine
authors.initials: C
authors.lastname: Desmedt
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Yates
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
authors.forename: Janina
authors.initials: J
authors.lastname: Kulka
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D015316:Genetic Therapy; D023281:Genomics; D006801:Humans; D051379:Mice; D009154:Mutation; D023041:Xenograft Model Antitumor Assays
chemical_list: D004273:DNA, Neoplasm
keywords: Breast cancer; Genomics; Progression; Sequencing