1.6.16 Cancer Cell Epigenome Definition

Cancer Cell Epigenome Definition is the description of the complete set of epigenetic marks, encompassing the genome-wide pattern of DNA methylation, the full complement of histone modifications, and the overall chromatin accessibility landscape, present across the entire genome of a given cancer cell, considered collectively as a single comprehensive profile. The cancer cell epigenome represents the totality of chemical and structural regulatory information layered on top of the cancer cell's DNA sequence, and it determines, in combination with that sequence, the complete pattern of gene expression exhibited by the cell.

Conceptual Basis of the Cancer Cell Epigenome

The Epigenome as a Genome-Wide Composite Profile

While a single epigenetic alteration or epimutation refers to a change at one specific locus, the epigenome refers to the complete, genome-wide collection of epigenetic information present across every locus simultaneously, providing a comprehensive picture of the regulatory state of the entire genome rather than a single gene or region.

Distinctness From the Underlying Genome

The cancer cell epigenome is conceptually distinct from the cancer cell genome, since the genome describes the sequence of nucleotides present in the DNA, whereas the epigenome describes the pattern of chemical modification and chromatin organization superimposed upon that same sequence, meaning that two cells with an identical genome sequence can nonetheless possess substantially different epigenomes.

Components of the Cancer Cell Epigenome

The Methylome Component

A central component of the cancer cell epigenome is its genome-wide pattern of DNA methylation, referred to as the methylome, which records the methylation status of cytosine bases across the entire genome and reveals both localized regions of abnormal hypermethylation and broader patterns of genome-wide hypomethylation characteristic of many cancer cells.

The Histone Modification Landscape

A further component of the cancer cell epigenome is the genome-wide distribution of the various chemical modifications present on histone tails, revealing which regions of the genome carry marks associated with open, active chromatin and which carry marks associated with condensed, silenced chromatin.

The Chromatin Accessibility Landscape

A further component of the cancer cell epigenome is the genome-wide map of chromatin accessibility, revealing which regions of the genome are physically open and available for protein binding and which regions remain shielded by dense nucleosome packaging.

Establishment of the Cancer Cell Epigenome

Inheritance From the Cell of Origin

The cancer cell epigenome does not arise from nothing but begins from the epigenome characteristic of the normal cell type from which the cancer originated, retaining many features of that original cellular identity while progressively accumulating abnormal alterations as the cancer develops.

Progressive Accumulation of Abnormal Alterations

As a cancer cell lineage develops and progresses, individual epigenetic alterations accumulate across the genome, gradually reshaping the overall epigenome away from the pattern characteristic of the original normal cell type and toward a pattern distinctive of the abnormal, malignant cellular state.

Significance of the Cancer Cell Epigenome Within Cancer Cell Biology

A Comprehensive Determinant of Gene Expression Alongside the Genome

The cancer cell epigenome, considered together with the underlying genome sequence, jointly determines the complete pattern of gene expression exhibited by a cancer cell, meaning that a full understanding of the abnormal behavior of a cancer cell requires consideration of both its genetic alterations and its epigenomic state.

A Basis for Characterizing and Classifying Tumors

Because the overall pattern of the cancer cell epigenome, including its characteristic patterns of hypermethylation, hypomethylation, and chromatin accessibility, can differ systematically between different cancer types and subtypes, comprehensive epigenomic profiling provides a further basis, distinct from genetic sequence analysis alone, for characterizing and classifying tumors according to their underlying molecular state.