Large hypomethylated blocks as a universal defining epigenetic alteration in human solid tumors

Area of Science:

• Cancer Epigenetics
• Genomics
• Tumor Biology

Background:

• Large hypomethylated blocks, associated with heterochromatic regions like LOCKs and LADs, have been observed in colorectal cancer.
• These blocks include single-copy genes and represent a novel observation in cancer epigenetics.

Purpose of the Study:

• To perform a comprehensive genome-scale analysis of hypomethylated blocks across various common solid human cancers.
• To investigate the presence and progression of these blocks in premalignant lesions and different clinical stages of cancer.

Main Methods:

• Genome-scale analysis using the Illumina HumanMethylation450 BeadChip platform.
• Application of a novel statistical approach for identifying large hypomethylated blocks.
• Analysis of diverse cancer types including breast, colon, lung, thyroid, and pancreas, along with premalignant lesions and matched normal tissues.

Main Results:

• Hypomethylated blocks are a universal feature of common solid human cancers, present from the earliest premalignant stages.
• These blocks are enriched with previously reported disrupted CpG islands, showing a flattened methylation signal.
• Genes with higher inter-individual expression variability are found within these hypomethylated blocks.

Conclusions:

• Hypomethylated blocks represent a universal epigenetic alteration in common solid human tumors.
• Their presence in premalignant lesions suggests a role in early cancer development.