title: The HER2 amplicon in breast cancer: Topoisomerase IIA and beyond.
abstract: HER2 gene amplification is observed in about 15% of breast cancers. The subgroup of HER2-positive breast cancers appears to be heterogeneous and presents complex patterns of gene amplification at the locus on chromosome 17q12-21. The molecular variations within the chromosome 17q amplicon and their clinical implications remain largely unknown. Besides the well-known TOP2A gene encoding Topoisomerase IIA, other genes might also be amplified and could play functional roles in breast cancer development and progression. This review will focus on the current knowledge concerning the HER2 amplicon heterogeneity, its clinical and biological impact and the pitfalls associated with the evaluation of gene amplifications at this locus, with particular attention to TOP2A and the link between TOP2A and anthracycline benefit. In addition it will discuss the clinical and biological implications of the amplification of ten other genes at this locus (MED1, STARD3, GRB7, THRA, RARA, IGFPB4, CCR7, KRT20, KRT19 and GAST) in breast cancer.
authors.affiliation: Service d'Oncologie Médicale, CRLC Val d'Aurelle-Paul Lamarque, Montpellier, F-34298, France. William.Jacot@montpellier.unicancer.fr
authors.forename: William
authors.initials: W
authors.lastname: Jacot
authors.forename: Maryse
authors.initials: M
authors.lastname: Fiche
authors.forename: Khalil
authors.initials: K
authors.lastname: Zaman
authors.forename: Anita
authors.initials: A
authors.lastname: Wolfer
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Lamy
mesh_terms: D000818:Animals; D018943:Anthracyclines / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D000075223:Poly-ADP-Ribose Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*
chemical_list: D018943:Anthracyclines; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C000618811:TOP2A protein, human