Retinoblastoma

Plus de détails

Viola (Cesario)

par Jessica Mannhaupt

Jupiter

par Аня Лузік

cell growth and division

par Bethany o

Life of Pi

par PT - 10 705591 TL Kennedy SS

A clonogenic assay is a cell biology technique for studying the effectiveness of specific agents on the survival and proliferation of cells.

Western Blot

Reverse Transcription quantitative real time PCR

3D

Heritable RB1-/- Retinoblastoma

One copy of the RB1 gene is damaged in all, or nearly all cells of the body. This is because the mutation was inherited from a parent, or happened very soon after conception. This is called a constitutional mutation.

Children with a constitutional RB1 mutation usually develop multiple tumours in both eyes, A small number of children have one or more tumours in only one eye.

Non-Heritable RB1-/- Retinoblastoma

Floating topic

This Paper is about Testing Survival Gene hypothesis

These people can only get Rb if second instance mutates RB1 through pt mutations OR intragenic deletions but DO NOT touch survival gene

large deletion may encompass a contiguous gene SURVIVAL GENE needed for Rb to work

Doesn't Make Sense

tumours

large germline deletions encompassing the entire RB1 locus could be associated with low or no tumor risk.

patients with germline chromosomal deletions of RB1

Multifocal - when more than one tumor is present in one eye

Unifocal - when a single RB tumor is present

Bilateral - when the tumors occur in both eyes

small percentage of retinoblastomas are caused by deletions in the region of chromosome 13 that contains the RB1 gene

therefor likely to develop a tumour

takes out only functional copy of gene that prevents uncontrollable cell growth

mutations of TS genes are dominant

3C

3B

3A

Subtopic

Loss of Heterozygosity

disease allele

if only functional copy mutate and no longer works

wt allele

normal function

LOH of RB1 gene

Each Cell has one fxnl copy

half the protein is not produced

still enough for cell functoin

RB1 defective

Multiple tumors arising in an individual patient with inherited retinoblastoma all were found to contain the same germ line mutation but had different somatic mutations affecting the remaining RB1 allele

Unilateral - when the tumors are present in one eye

helps regulate cell cycle

prevents premature entry into S phase

second somatic inactivating mutation

Tumour Development

predisposition to Rb

xenografts

Grafts between individuals of different species—xenografts or heterografts—are usually destroyed very quickly by the recipient

orthotopic

Tissue or organ grafts may be transplanted to their normal situation in the recipient and are then known as orthotopic—for example, skin to the surface of the body.

Hereditary Rb

RB1

tumour suppressor gene

mutation in RB1

single retinal cell

It represents the most common pediatric intraocular neoplasm, which in virtually every case results from the inactivation of both alleles of the RB1 tumor suppressor gene in the developing retina

This is a test note

survival gene in retinoblastoma

Cell survival genes identified. By switching off, one by one, almost 18,000 genes — about 90 per cent of the entire human genome — scientists have identified the genes that are essential for cell survival. This could improve our understanding of which genes are most important in diseases like cance

in vitro

in vivo orthotopic xenograft models

RB1 -/-

a subunit of the mediator complex.

MED4

In this study, we define a minimal genomic region associated with this low penetrance

Genomic Region

RB1 allele

RB1 gene encodes for a protein called Rb protein or pRb

The RB1 gene provides instructions for making a protein called pRB. This protein acts as a tumor suppressor, which means that it regulates cell growth and keeps cells from dividing too fast or in an uncontrolled way. Under certain conditions, pRB stops other proteins from triggering DNA replication, the process by which DNA makes a copy of itself. Because DNA replication must occur before a cell can divide, tight regulation of this process controls cell division and helps prevent the growth of tumors. Additionally, pRB interacts with other proteins to influence cell survival, the self-destruction of cells (apoptosis), and the process by which cells mature to carry out special functions (differentiation).

multiple retinoblastoma

Familial Retinoblastoma

germline mutation

another synthetic lethal target

"Trilateral" - the occurrence of bilateral RB plus a pinealoma

Retinoblastoma

RB1 tumor suppressor gene