title: LINE-1 hypermethylation in peripheral blood of cutaneous melanoma patients is associated with metastasis.
abstract: Aberrant DNA methylation pattern is a well-known epigenetic marker of cancer cells. Recently, aberrant methylation was also reported in the peripheral blood of cancer patients and it could potentially serve as a biomarker for cancer risk. We investigated the methylation pattern of LINE-1 and other repetitive DNA elements in peripheral blood of cutaneous melanoma patients in order to search for an association with clinical characteristics. The patient cohort was composed by 69 unrelated melanoma patients, 28 of whom were hereditary cases (with or without CDKN2A mutations) and 41 were isolated (sporadic) melanoma cases. Methylation of LINE-1 was evaluated by pyrosequencing, whereas additional repetitive DNA sequences were assessed using Illumina 450K methylation microarray. Melanoma patients exhibited a higher, albeit heterogeneous, LINE-1 methylation level compared with controls. Hereditary melanoma patients carrying CDKN2A mutations showed a hypermethylated pattern of both LINE-1 and repetitive DNA elements compared with other patients. In particular, the methylation level at one specific CpG of LINE-1 was found to be correlated with the occurrence of metastasis. Our data suggest that LINE-1 hypermethylation in peripheral blood of melanoma patients is a potential epigenetic biomarker for metastasis occurrence.
authors: aInternational Research Center bDepartment of Oncogenetics cSkin Cancer Department, A. C. Camargo Cancer Center dDepartment of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo eFederal Technological University of Paraná, Paraná, Brazil.
authors: Érica S S
authors: ÉS
authors: De Araújo
authors: André Y
authors: AY
authors: Kashiwabara
authors: Maria I W
authors: MI
authors: Achatz
authors: Luciana F
authors: LF
authors: Moredo
authors: Bianca C S
authors: BC
authors: De Sá
authors: João P
authors: JP
authors: Duprat
authors: Carla
authors: C
authors: Rosenberg
authors: Dirce M
authors: DM
authors: Carraro
authors: Ana C V
authors: AC
authors: Krepischi
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D008545:Melanoma / Q000097:blood / Q000235:genetics* / Q000556:secondary*; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor
references: Cancer Prev Res (Phila). 2012 Dec;5(12):1345-57
references: 23135621
references: Int J Cancer. 2010 Oct 15;127(8):1866-74
references: 20099281
references: Mob Genet Elements. 2011 Jul;1(2):122-127
references: 22016860
references: Cancer Epidemiol Biomarkers Prev. 2013 Mar;22(3):348-55
references: 23300023
references: Annu Rev Biochem. 2005;74:481-514
references: 15952895
references: Int J Cancer. 2012 Mar 1;130(5):1151-9
references: 21445976
references: Genome Biol. 2014;15(2):R31
references: 24495553
references: Exp Mol Pathol. 2014 Dec;97(3):425-32
references: 25236571
references: PLoS Genet. 2009 Aug;5(8):e1000602
references: 19680444
references: Epigenetics. 2013 Jul;8(7):748-55
references: 23804018
references: Cell Mol Life Sci. 2014 Mar;71(6):1017-32
references: 24114325
references: J Zhejiang Univ Sci B. 2011 Oct;12(10):805-11
references: 21960343
references: PLoS One. 2012;7(4):e34615
references: 22509334
references: PLoS One. 2011;6(11):e27361
references: 22076155
references: PLoS One. 2013;8(11):e79044
references: 24260150
references: Hum Genet. 2009 Oct;126(4):499-510
references: 19585149
references: N Engl J Med. 1998 Mar 26;338(13):879-87
references: 9516223
references: Melanoma Res. 2013 Feb;23(1):55-60
references: 23222549
references: PLoS One. 2011;6(1):e16252
references: 21311577
references: Adv Genet. 2010;70:27-56
references: 20920744
references: Methods Mol Biol. 2014;1102:481-99
references: 24258994