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01.08.2012 | Preclinical Study

Hypomethylation of LINE-1 in primary tumor has poor prognosis in young breast cancer patients: a retrospective cohort study

verfasst von: Anneke Q. van Hoesel, Cornelis J. H. van de Velde, Peter J. K. Kuppen, Gerrit Jan Liefers, Hein Putter, Yusuke Sato, David A. Elashoff, Roderick R. Turner, Jaime M. Shamonki, Esther M. de Kruijf, Johanna G. H. van Nes, Armando E. Giuliano, Dave S. B. Hoon

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2012

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Abstract

Long interspersed element 1 (LINE-1), a non-coding genomic repeat sequence, methylation status can influence tumor progression. In this study, the clinical significance of LINE-1 methylation status was assessed in primary breast cancer in young versus old breast cancer patients. LINE-1 methylation index (MI) was assessed by absolute quantitative assessment of methylated alleles (AQAMA) PCR assay. Initially, LINE-1 MI was assessed in a preliminary study of 235 tissues representing different stages of ductal breast cancer development. Next, an independent cohort of 379 primary ductal breast cancer patients (median follow-up 18.9 years) was studied. LINE-1 hypomethylation was shown to occur in DCIS and invasive breast cancer. In primary breast cancer it was associated with pathological tumor stage (p = 0.026), lymph node metastasis (p = 0.022), and higher age at diagnosis (>55, p < 0.001). In multivariate analysis, LINE-1 hypomethylation was associated with decreased OS (HR 2.19, 95 % CI 1.17–4.09, log-rank p = 0.014), DFS (HR 2.05, 95 % CI 1.14–3.67, log-rank p = 0.016) and increased DR (HR 2.83, 95 % CI 1.53–5.21, log-rank p = 0.001) in younger (≤55 years), but not older patients (>55 years). LINE-1 analysis of primary breast cancer demonstrated cancer-related age-dependent hypomethylation. In patients ≤55 years, LINE-1 hypomethylation portends a high-risk of DR.

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Titel: Hypomethylation of LINE-1 in primary tumor has poor prognosis in young breast cancer patients: a retrospective cohort study
verfasst von: Anneke Q. van Hoesel
Cornelis J. H. van de Velde
Peter J. K. Kuppen
Gerrit Jan Liefers
Hein Putter
Yusuke Sato
David A. Elashoff
Roderick R. Turner
Jaime M. Shamonki
Esther M. de Kruijf
Johanna G. H. van Nes
Armando E. Giuliano
Dave S. B. Hoon
Publikationsdatum: 01.08.2012
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 3/2012
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-012-2038-0

Springer Medizin

Hypomethylation of LINE-1 in primary tumor has poor prognosis in young breast cancer patients: a retrospective cohort study

Abstract

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