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Exp Mol Pathol. 2014 Dec;97(3):425-32. doi: 10.1016/j.yexmp.2014.09.009. Epub 2014 Sep 16.

Genome-wide DNA methylation profile of leukocytes from melanoma patients with and without CDKN2A mutations.

Author information

1
International Center for Research, A. C. Camargo Cancer Center, Sao Paulo, Brazil.
2
International Center for Research, A. C. Camargo Cancer Center, Sao Paulo, Brazil; Institute of Mathematics and Statistics, University of Sao Paulo, Sao Paulo, Brazil.
3
Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil.
4
Institute of Mathematics and Statistics, University of Sao Paulo, Sao Paulo, Brazil.
5
International Center for Research, A. C. Camargo Cancer Center, Sao Paulo, Brazil; Department of Oncogenetics, A. C. Camargo Cancer Center, Sao Paulo, Brazil.
6
Department of Skin Cancer, A. C. Camargo Cancer Center, Sao Paulo, Brazil.
7
Department and Institute of Psychiatry, Medical School, University of Sao Paulo, Sao Paulo, Brazil.
8
International Center for Research, A. C. Camargo Cancer Center, Sao Paulo, Brazil; Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: ana.krepischi@gmail.com.

Abstract

Melanoma is a highly aggressive cancer, accounting for up to 75% of skin cancer deaths. A small proportion of melanoma cases can be ascribed to the presence of highly penetrant germline mutations, and approximately 40% of hereditary melanoma cases are caused by CDKN2A mutations. The current study sought to investigate whether the presence of germline CDKN2A mutations or the occurrence of cutaneous melanoma would result in constitutive genome-wide DNA methylation changes. The leukocyte methylomes of two groups of melanoma patients (those with germline CDKN2A mutations and those without CDKN2A mutations) were analyzed together with the profile of a control group of individuals. A pattern of DNA hypomethylation was detected in the CDKN2A-negative patients relative to both CDKN2A-mutated patients and controls. Additionally, we delineated a panel of 90 CpG sites that were differentially methylated in CDKN2A-mutated patients relative to controls. Although we identified a possible constitutive epigenetic signature in CDKN2A-mutated patients, the occurrence of reported SNPs at the detected CpG sites complicated the data interpretation. Thus, further studies are required to elucidate the impact of these findings on melanoma predisposition and their possible effect on the penetrance of CDKN2A mutations.

KEYWORDS:

CDKN2A; DNA methylation; Leukocytes; Melanoma; melanoma epigenetics

PMID:
25236571
DOI:
10.1016/j.yexmp.2014.09.009
[Indexed for MEDLINE]
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