Quantification and clinical relevance of gene amplification at chromosome 17q12-q21 in human epidermal growth factor receptor 2-amplified breast cancers
Autor: | Frédéric Fina, Caroline Bascoul-Mollevi, Anne-Claire Laberenne, L'Houcine Ouafik, William Jacot, Pierre-Jean Lamy, Pierre-Marie Martin |
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Přispěvatelé: | Centre régional de lutte contre le cancer [CRLCC], Laboratoire de Transfert d'Oncologie Biologique [Hôpital Nord - APHM], Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Unité de biostatistiques, CRLCC Val d'Aurelle - Paul Lamarque, Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Service d'oncologie médicale [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ouafik, L'Houcine |
Jazyk: | angličtina |
Předmět: |
Adult
Amplification Level Receptor ErbB-2 [SDV.CAN]Life Sciences [q-bio]/Cancer Breast Neoplasms Kaplan-Meier Estimate Biology TOP2A Deletion 03 medical and health sciences 0302 clinical medicine Breast cancer [SDV.CAN] Life Sciences [q-bio]/Cancer Surgical oncology [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Gene duplication Freeze Tumor Specimen medicine Humans Clinical significance Receptors Somatostatin Overall Survival Rate skin and connective tissue diseases Gene 030304 developmental biology Aged Neoplasm Staging Medicine(all) 0303 health sciences TOP2A Amplification Gene Expression Profiling GRB7 Gene Amplification Chromosome Middle Aged medicine.disease 3. Good health Gene expression profiling Gene Expression Regulation Neoplastic 030220 oncology & carcinogenesis Cancer research biology.protein [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Female Research Article Chromosomes Human Pair 17 Follow-Up Studies |
Zdroj: | Breast Cancer Research : BCR Breast Cancer Research Breast Cancer Research, BioMed Central, 2011, 13, pp.R15. ⟨10.1186/bcr2824⟩ Breast Cancer Research, vol. 13, no. 1, pp. R15 |
ISSN: | 1465-542X 1465-5411 |
DOI: | 10.1186/bcr2824 |
Popis: | International audience; Introduction: Human epidermal growth factor receptor 2 (HER2)-amplified breast cancers represent a tumor subtype with chromosome 17q rearrangements that lead to frequent gene amplifications. The aim of this study was to quantify the amplification of genes located on chromosome 17q and to analyze the relations between the pattern of gene amplifications and the patients' characteristics and survival.Methods: Patients with HER2-positive breast tumors (HER2 score of 3+ by immunohistochemistry or positive for HER2 amplification by fluorescence in situ hybridization (FISH)) (n = 86) and with HER2-negative breast tumors (n = 40) (negative controls) were included in this study. Using a quantitative polymerase chain reaction method and DNA extracted from frozen tumor specimens, 11 genes (MED1, STARD3, HER2, GRB7, THRA, RARA, TOP2A, IGFBP4, CCR7, KRT20, KRT19 and GAS), which are localized within Chr17q12-q21 and have a putative role in breast cancer development, were quantified. Relapse-free and overall survival rates were estimated from the date of surgery to the date of the event of interest (recurrence or death) using the Kaplan-Meier method.Results: Gene amplification was observed only in HER2-positive tumors, and the frequency of amplification decreased with the distance of the gene from HER2. HER2 presented the highest level of amplification. TOP2A was not included in the smallest region of amplification involving HER2. Amplification of RARA, KRT20 and KRT19 was significantly associated with node-positive breast cancer (P = 0.030, P = 0.002 and P = 0.033, respectively). During a median follow-up period of 55 months (range, 6 to 81 months), the subgroup of patients with hormone receptor-negative cancer and without TOP2A amplification showed the worst survival (relapse-free survival: hazard ratio (HR) = 0.29, 95% confidence interval (95% CI), 0.13 to 0.65, P = 0.001; and overall survival: HR = 0.28, 95% CI, 0.10 to 0.76, P = 0.008).HER2 amplification seems to drive genomic instability along chromosome 17q, leading to different patterns of gene amplification. This study confirms the clinical importance of identifying, among patients with HER2-positive breast tumors, the subgroup of patients with hormone receptor-negative and nonamplified TOP2A cancers as they have the worst prognosis. |
Databáze: | OpenAIRE |
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