Epigenetics in Human Diseases and
Cancer Questions and answers
Key players of genome organization
Chromatin loops, spatial chromosome organization, chromosome translocations.
Spatial clustering of genes
Facilitates expression by enabling shared transcription and processing sites, interactions with distal
regulatory elements, and proximity of chromosomes.
Local organization of chromatin loops
Essential for cell type-specific gene expression and chromatin remodeling during development and
differentiation.
SATB1
Folds and remodels chromatin, promotes tumor growth by genome reprogramming, and regulates T cell
activation.
CTCF
Acts as a global genome organizer and insulator, influencing gene expression and imprinting.
HP1
Binds to histone H3K9Me3 for gene silencing and heterochromatin formation.
Three basic steps to form a translocation
1) DNA double strand breaks 2) Physical association of broken ends 3) Rejoining of partner
chromosomes.
Higher translocation frequency
Translocations preferentially occur between proximally positioned chromosomes.
Breakage susceptibility factors
Facilitated by DNA sequence features, chromatin structure and histone modifications.
Changes linked to chromosome rearrangement
Deletions, inversions and translocations.
Differences between Angelman and Prader-Willi syndromes
Results from defects in an imprinted region. Angelman: Paternal disomy leads to loss of maternal UBE3A
function. Prader-Willi Syndrome: Maternal disomy leads to loss of paternal gene expression.
, Symptoms of Beckwith-Wiedemann
Overgrowth, enlarged tongue, abdominal wall defects, increased cancer risk due to loss of maternal
imprinting at H19/IGF2.
Causes of Wilms' tumor
Loss of imprinting of IGF2, H19 and methylation of H19 promoter.
Causes of Silver-Russell syndrome
- IGF2 , - methylation at ICR + H19 Maternal uniparental disomy of chromosome 7.
Definition of cancer
Clonal disease characterized by loss of proliferation control, cellular identity, and abnormal
differentiation.
Mechanisms causing heritable disruptions
Activation of oncogenes and inactivation of tumor suppressor genes.
Epigenetic mechanisms of cancer stem cell formation
1) Local epigenetic changes in normal stem cells that affect control and self renewal 2) Global epigenetic
changes that induce reprogramming of differentiated cell.
Two- or multiple-hit hypothesis
Describes how DNA methylation can contribute to the inactivation of tumor suppressor genes.
Tumor Suppressor Gene Inactivation
Both alleles of a tumor suppressor gene must be inactivated by genetic or epigenetic events in a
malignant cell line.
Methylation
Methylation can induce gene inactivation or gene silencing of tumor suppressor genes.
Cooperation of Abnormalities
A cooperation between genetic and epigenetic abnormalities drives the initiation and progression of
cancer.
Epigenetic Gatekeeper Hypothesis
Gene silencing of epigenetic gatekeepers (genes hypermethylated in invasive stages of cancer) blocks
differentiation and allows abnormal survival and clonal expansion of cells.
Properties of Malignant Neoplasms
High heterogeneity, resistance to therapies, and stem-like properties of cancer cells make malignant
neoplasms very difficult to treat.
Cancer Questions and answers
Key players of genome organization
Chromatin loops, spatial chromosome organization, chromosome translocations.
Spatial clustering of genes
Facilitates expression by enabling shared transcription and processing sites, interactions with distal
regulatory elements, and proximity of chromosomes.
Local organization of chromatin loops
Essential for cell type-specific gene expression and chromatin remodeling during development and
differentiation.
SATB1
Folds and remodels chromatin, promotes tumor growth by genome reprogramming, and regulates T cell
activation.
CTCF
Acts as a global genome organizer and insulator, influencing gene expression and imprinting.
HP1
Binds to histone H3K9Me3 for gene silencing and heterochromatin formation.
Three basic steps to form a translocation
1) DNA double strand breaks 2) Physical association of broken ends 3) Rejoining of partner
chromosomes.
Higher translocation frequency
Translocations preferentially occur between proximally positioned chromosomes.
Breakage susceptibility factors
Facilitated by DNA sequence features, chromatin structure and histone modifications.
Changes linked to chromosome rearrangement
Deletions, inversions and translocations.
Differences between Angelman and Prader-Willi syndromes
Results from defects in an imprinted region. Angelman: Paternal disomy leads to loss of maternal UBE3A
function. Prader-Willi Syndrome: Maternal disomy leads to loss of paternal gene expression.
, Symptoms of Beckwith-Wiedemann
Overgrowth, enlarged tongue, abdominal wall defects, increased cancer risk due to loss of maternal
imprinting at H19/IGF2.
Causes of Wilms' tumor
Loss of imprinting of IGF2, H19 and methylation of H19 promoter.
Causes of Silver-Russell syndrome
- IGF2 , - methylation at ICR + H19 Maternal uniparental disomy of chromosome 7.
Definition of cancer
Clonal disease characterized by loss of proliferation control, cellular identity, and abnormal
differentiation.
Mechanisms causing heritable disruptions
Activation of oncogenes and inactivation of tumor suppressor genes.
Epigenetic mechanisms of cancer stem cell formation
1) Local epigenetic changes in normal stem cells that affect control and self renewal 2) Global epigenetic
changes that induce reprogramming of differentiated cell.
Two- or multiple-hit hypothesis
Describes how DNA methylation can contribute to the inactivation of tumor suppressor genes.
Tumor Suppressor Gene Inactivation
Both alleles of a tumor suppressor gene must be inactivated by genetic or epigenetic events in a
malignant cell line.
Methylation
Methylation can induce gene inactivation or gene silencing of tumor suppressor genes.
Cooperation of Abnormalities
A cooperation between genetic and epigenetic abnormalities drives the initiation and progression of
cancer.
Epigenetic Gatekeeper Hypothesis
Gene silencing of epigenetic gatekeepers (genes hypermethylated in invasive stages of cancer) blocks
differentiation and allows abnormal survival and clonal expansion of cells.
Properties of Malignant Neoplasms
High heterogeneity, resistance to therapies, and stem-like properties of cancer cells make malignant
neoplasms very difficult to treat.
