Question

Explain the figures below

METHYLATION IMBALANCE may contribute to TUMOR PROGRESSION GLOBAL HYPOMETHYLATION DNA HYPERMETHYLATION Observed in neoplastic cells Inactivation of tumor- suppressor genes: p16, BRCA1 May induce neoplastic transformation Inactivation of DNA repair genes: MLH1, MGMT Genomic instability, Abnormal chromosomal structures and Activating oncogenes.

Answer 1

Dear student ,

According to my knowledge on cancer research,

Figure 1:

For most of the mutations to occur , methylation plays an important role.

Improper methylation ,may lead to formation of tumors.

For GLOBAL HYPOMETHYLATION ,

It is particularly observed in neoplastic cells ,

thus considered as one of the most important feature of malignancy.  

In this case , a loss of methy group in 5-methylcytosine nucleotide occurs. (Methylation is a natural process... but in case of mammals , the cytosine methylation is followed by guanine methylation)

These abnormal changes may lead to certain complications such as mentioned in the diagram- viz genomic instability, annormal chromosomal structure or many more.

But incase of DNA HYPERMETHYLATION :

This is a natural method , wherein methyl groups are added to the DNA strands , thus changing the activity of DNA segment ,without altering any sequence.

Hypermethylation may lead to abnormal dna repair mechanisms.

Viz, inactivation of tumor suppressor genes , inactivation of DNA repair genes , oncogene activation, etc.

Thus , this leads to cancerous outcomes.

To be noted:

Hypomethylation occurs in earlier stages, mostly during pregnancy, or fetus formation , finally may lead to loss of imprinting.But hypermethylation may occur in secondary stages of life.

Present researchers have claimed that these are completely independent of each other depending upon cancer type (reviewed by Peter Molly , 2007).