Preneoplastic Alterations Define CLL DNA Methylome and Persist through Disease Progression and Therapy.

ABSTRACT: Most human cancers converge to a deregulated methylome with reduced global levels and elevated methylation at select CpG islands. To investigate the emergence and dynamics of the cancer methylome, we characterized genome-wide DNA methylation in pre-neoplastic monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), including serial samples collected across disease course. We detected the aberrant tumor-associated methylation landscape at CLL diagnosis and found no significantly differentially methylated regions in the high-count MBL-to-CLL transition. Patient methylomes showed remarkable stability with natural disease and post-therapy progression. Single CLL cells were consistently aberrantly methylated, indicating a homogeneous transition to the altered epigenetic sta

SUBMITTER: Kretzmer H 

PROVIDER: S-EPMC7888194 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature