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Epigenetic Control of Genes Involved in Cancer Initiation and Progression

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Epigenetic Advancements in Cancer

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Abstract

Aberrant changes in gene expression that regulate the cell cycle, cell division and cell death are major contributing factors to the genesis of tumors. Tumors arising from heritable epigenetic changes governed by epigenetic mechanisms are treatable by the use of compounds that reverses the epigenetic change, as the DNA sequence remains unaltered. DNA methylation and histone modifications are primary mechanisms that induce epigenetic changes and are well studied. Micro RNAs, which are about 20–25 nucleotides long RNA sequence, are also emerging as important epigenetic regulators in tumorigenesis. As evident in many cancers, tumors are heterogeneous in nature and therefore a common epigenetic signature that dictates the onset or the progression of the diseases is hard to determine. In addition to tumor heterogeneity, epigenetic processes are highly dynamic and therefore rather than single epigenetic events, the combination of epigenetic patterns obviate the changes. However, most tumors strongly exhibit epigenetic dysfunctions of genes crucial to the cell cycle. The analysis of epigenetic changes, degree of the change and reversal of epigenetic alterations is important to the diagnosis, prognosis and therapeutics of various cancers. The goal of this chapter is to discuss genes that are susceptible to aberrant epigenetic modifications and the influence of the altered epigenetic states in tumorigenesis. The assessment and detection of epigenetic patterns, degree of methylation of genes involved in tumorigenesis as potential biomarkers for the diagnosis and prognosis of the disease will also be presented.

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Abbreviations

ADAM19:

A Disintegrin And Metalloproteinase Domain 19

ADAM12-L:

A Disintegrin And Metalloproteinase Domain 12

AICDA:

Activation-Induced Cytidine Deaminase

APC:

Adenomatous polyposis coli

AKT:

v-akt murine thymoma

ALX4:

Aristaless-Like Homeobox 4

ATG7:

Autophagy 7-Like

BCL2L11:

BCL2-Like 11

BRCA1:

Breast cancer 1

BRCA2:

Breast cancer 2

CRC:

Colorectal cancer

c-Myc:

V-myc avian myelocytomatosis

CDKN2A:

Cyclin-dependent kinase inhibitor 2A

DNMT1:

DNA methyltransferase 1

DNMT3A:

DNA methyltransferase 3A

DNMT3B:

DNA methyltransferase 3B

EpCAM:

Epithelial cell adhesion molecule

ER:

Estrogen receptor

E2F1:

E2F transcription factor 1

ERG:

ETS-related gene

EOC:

Epithelial ovarian cancers

ERK:

Extracellular signal-regulated kinases

ESCC:

Esophageal squamous cell carcinomas

ERK5:

Extracellular-signal-regulated kinase 5

Gli3:

GLI Family Zinc Finger 3

hTERT:

Human telomerase reverse transcriptase

HATs:

Histone acetylases

HCC:

Hepatocellular carcinomas

HNF4 γ:

Hepatocyte nuclear factor 4 receptor γ

HDACs:

Histone deacetylases

H3-K9:

Histone H3 Lysine 9

H3-K27:

Histone H3 lysine 27

INK4A:

Inhibitor of Kinases

IGFBP2:

Insulin-Like Growth Factor Binding Protein 2

ITCH:

Itchy E3 Ubiquitin Protein Ligase

KPNB1:

Karyopherin Subunit Beta-1

LIN28:

Lin-28 homolog A

MMP3:

Matrix Metallopeptidase 3

mTOR:

Mechanistic Target Of Rapamycin

MERTK:

MER Receptor Tyrosine Kinase

MSP:

Methyl sensitive PCR

MAPK:

Mitogen activated protein kinases

Mekk2:

Mitogen-Activated Protein Kinase Kinase 2

Mekk5:

Mitogen-Activated Protein Kinase Kinase 5

Mad1:

Mitotic arrest deficient 1

MDR-1:

Multidrug resistance-1

MiRs:

Micro RNAs

MTS-1:

Multiple tumor suppressor

NPC:

Nasopharyngeal carcinomas

NSCLC:

Non-small cell lung carcinoma

Notch 1:

Notch Homolog 1

NR2F2:

Nuclear Receptor Subfamily 2 Group F, Member 2

oncomiRs:

Oncogene

PI3K:

Phosphatidylinositol-4,5-Bisphosphate 3-Kinase

PTEN:

Phosphatase and Tensin homologue deleted from chromosome 10

PCa:

Prostate cancer

PIPNC1:

PTEN Induced Putative Kinase 1

PAK4:

P21 (CDKN1A)-Activated Kinase 4

RASSF:

Ras-association domain family

Rb:

Retinoblastoma protein

RECK:

Reversion-Inducing-Cysteine-Rich Protein with Kazal Motifs

SPARC:

Secreted Protein Acidic, Cysteine-Rich

SEPT9:

Septin 9

SMAD4:

SMAD Family Member 4

SNAI1:

Snail Family Zinc Finger

TIMP:

Tissue Inhibitor of Metalloproteinases

TP53:

Tumor protein p53

tsmiRs:

Tumor suppressor

ZEB 1:

zinc finger E-box binding homeobox 1

ZEB 2:

zinc finger E-box binding homeobox 1

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  1. Department of Biological Sciences, Life Science Building, Alabama State University, Montgomery, AL, 36104, USA

    Sabita N. Saldanha & Shivani Soni

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  1. Sabita N. Saldanha
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Correspondence to Sabita N. Saldanha .

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  1. Department of Biological Sciences, Alabama State University, Montgomery, Alabama, USA

    Manoj K. Mishra

  2. School of Medicine, Washington University, St. Louis, Missouri, USA

    Kumar S. Bishnupuri

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Saldanha, S.N., Soni, S. (2016). Epigenetic Control of Genes Involved in Cancer Initiation and Progression. In: Mishra, M., Bishnupuri, K. (eds) Epigenetic Advancements in Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-24951-3_1

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