Integrating methylome and transcriptome signatures expands the molecular classification of the pituitary tumors

Abnormal DNA methylation contributes to tumor progression and is emerging as a prognostic marker in several types of cancers. Pituitary tumors (PitNETs) tumorigenesis is still not completely understood. Few studies have integrated exome, methylome, and transcriptome analyses. Taking advantage of a comprehensive phenotypic characterized Brazilian cohort, which has heterogeneous ethnic origin, we combined methylome and transcriptome analysis of the three major subtypes of surgically resectable PitNETs (n = 77): GH-secreting (acromegaly, n = 18), ACTH-secreting (Cushing disease, n = 13), and non-functioning (n = 46) PitNETs. Here, we included methylome and basal patient / tumor data. Retrospective cross-sectional study. DNA from 77 microdissected, fresh frozen pituitary tumor samples from patients was extracted using the QIAamp DNA Mini Kit (QIAGEN, Hilden, Germany) according to the manufacturer's instruction. DNA was commisioned to the University of Southern California Keck Genomics Platform (Los Angeles, CA, USA), where it was bisulfite-converted using tht EZ DNA methylation kit (Zymo Research, Irvine, CA) , as provided by the manufacturer, and hybridized to the Illumina Infinium HumanMethylation850 BeadChip as specified by Illumina.