title: Leukocyte DNA as surrogate for the evaluation of imprinted Loci methylation in mammary tissue DNA.
abstract: There is growing interest in identifying surrogate tissues to identify epimutations in cancer patients since primary target tissues are often difficult to obtain. Methylation patterns at imprinted loci are established during gametogenesis and post fertilization and their alterations have been associated with elevated risk of cancer. Methylation at several imprinted differentially methylated regions (GRB10 ICR, H19 ICR, KvDMR, SNRPN/SNURF ICR, IGF2 DMR0, and IGF2 DMR2) were analyzed in DNA from leukocytes and mammary tissue (normal, benign diseases, or malignant tumors) from 87 women with and without breast cancer (average age of cancer patients: 53; range: 31-77). Correlations between genomic variants and DNA methylation at the studied loci could not be assessed, making it impossible to exclude such effects. Methylation levels observed in leukocyte and mammary tissue DNA were close to the 50% expected for monoallellic methylation. While no correlation was observed between leukocyte and mammary tissue DNA methylation for most of the analyzed imprinted genes, Spearman's correlations were statistically significant for IGF2 DMR0 and IGF2 DMR2, although absolute methylation levels differed. Leukocyte DNA methylation levels of selected imprinted genes may therefore serve as surrogate markers of DNA methylation in cancer tissue.
authors: Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Ludovic
authors: L
authors: Barault
authors: Rachel E
authors: RE
authors: Ellsworth
authors: Holly R
authors: HR
authors: Harris
authors: Allyson L
authors: AL
authors: Valente
authors: Craig D
authors: CD
authors: Shriver
authors: Karin B
authors: KB
authors: Michels
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D018899:CpG Islands; D004247:DNA / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D056426:Genetic Loci; D018392:Genomic Imprinting; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D042361:Mammary Glands, Human / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D055815:Young Adult
chemical_list: D004247:DNA