IMBICE   05372
INSTITUTO MULTIDISCIPLINARIO DE BIOLOGIA CELULAR
Unidad Ejecutora - UE
artículos
Título:
LINE-1 hypomethylation in familial and sporadic cancer
Autor/es:
PAVICIC, W.; JOENSUU EI.; NIEMINEN T.; PELTOMÄKI P.
Revista:
JOURNAL OF MOLECULAR MEDICINE (BERLIN, GERMANY)
Editorial:
SPRINGER
Referencias:
Lugar: Berlin; Año: 2012 vol. 90 p. 827 - 835
ISSN:
0946-2716
Resumen:
Increased and decreased methylation at specific sequences
(hypermethylation and hypomethylation, respectively) is characteristic
of tumor DNA compared to normal DNA and promotes carcinogenesis in
multiple ways including genomic instability. Long interspersed element
(LINE), an abundant class of retrotransposons, provides a surrogate
marker for global hypomethylation. We developed methylation-specific
multiplex ligation-dependent probe amplification assays to study LINE-1
methylation in cases of colorectal, gastric, and endometrial cancer
(N = 276), stratified by patient category [sporadic; Lynch syndrome
(LS); familial colorectal cancer type X (FCCX)] and microsatellite
instability status. Within each patient group, LINE-1 showed lower
methylation in tumor DNA relative to paired normal DNA and
hypomethylation was statistically significant in most cases.
Interestingly, normal colorectal mucosa samples from different patient
groups displayed differences in LINE-1 methylation that mirrored
differences between the respective tumor tissues, with a decreasing
trend for LINE-1 methylation from patients with sporadic colorectal
cancer to LS to FCCX. Despite the fact that the degree of LINE-1
methylation is generally tissue specific, normal colorectal mucosa,
gastric mucosa, and endometrium from LS patients showed similar levels
of LINE-1 methylation. Our results suggest that the degree of LINE-1
methylation may constitute a "field defect" that may predispose normal
tissues for cancer development.