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
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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