Question

Fine detail required please!

1) Discuss how fusion genes can originate from chromosomal breaks, and how these fusion genes can lead to cancer

b) Within your answer, please discuss in detail the genotype, and how this leads to the phenotype of at least one type of cancer

c) discuss the genetic screening techniques that can be used to assess this disorder, and any recent developments in this area

d) discuss how a detailed understanding of the genotype could lead to novel therapeutics for cancers originating from fusion genes Please give detailed answer important assesment

Answer 1

a)When a chromosome breaks there is the formation of bridges.This is formed because after the breakage the chromosomes tend to fuse and thus forming a bridge.This may result in invetion of chromosome or interstitial deletions or other changes in the region.This fusion usually results in the formation fusion genes where a hybrid gene is formed as a result of this process .

Since fusion gene contain a hydrid or blend of different unrelated gene, this process of transription and translation are highly disrupted and this change in the expressionof these genes can lead to changes resulting in malignancy or cancer.

b)An example of this fusion gene scenario is described below:

Many cancers of the thyroid is caused by the fusion of RET with CCDC6.This causes cancer by overexpressing proteins which activates the RAS and MAPK pathway.

c)The genetic screening in case of these tumors is mainly carried out by the chromosome banding analysis which is usually followed by RT-PCR or Sanger sequencing methods.

In banding analysis the chromosomes are stained and are karyotyped and by this method any abnormalities in the arrangement or size or shape may be detected which serves as an initial indicative of gene fusion.Later amplification may be done by the RT-PCR and Sanger sequencing thereby providing a better picture and understanding and effects of the fusion on DNA.

Newer methods include Next Generation Sequencing.

d)The fusions result in the change in genetic structure and can cause the deletions , additions or various other mutations.A deep understanding of the genetic aspect is necessary because similar effects occur to the cancerous cells and by understanding these genotypes we can analyse the development of cancers and also can design various therapy related approches to inbit this process at every step possible.