DNA methylation and gene deletion analysis of brain metastases in melanoma patients identifies mutually exclusive molecular alterations.

ABSTRACT:

Background

The brain is a common target of metastases for melanoma patients. Little is known about the genetic and epigenetic alterations in melanoma brain metastases (MBMs). Unraveling these molecular alterations is a key step in understanding their aggressive nature and identifying novel therapeutic targets.

Methods

Genome-wide DNA methylation analyses of MBMs (n = 15) and normal brain tissues (n = 91) and simultaneous multigene DNA methylation and gene deletion analyses of metastatic melanoma tissues (99 MBMs and 43 extracranial metastases) were performed. BRAF and NRAS mutations were evaluated in MBMs by targeted sequencing.

Results

MBMs showed significant epigenetic heterogeneity. RARB, RASSF1, ESR1, APC, PTEN, and CDH13 genes were frequently hypermethylated. Del

SUBMITTER: Marzese DM 

PROVIDER: S-EPMC4201072 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature