Retinoblastoma

RB1 tumor suppressor gene

RB1 tumor suppressor gene

Familial Retinoblastoma

germline mutation

another synthetic lethal target

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

RB1 allele

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RB1 gene encodes for a protein called Rb protein or pRbThe 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

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

Genomic Region

MED4

a subunit of the mediator
complex.

RB1 -/-

in vivo orthotopic xenograft models

in vitro

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

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

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This is a test note

mutation in RB1

single retinal cell

Hereditary Rb

RB1

tumour suppressor gene

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.

xenografts

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

predisposition to Rb

Tumour Development

second somatic inactivating mutation

prevents premature entry into S phase

helps regulate cell cycle

RB1 defective

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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

half the protein is not produced

still enough for cell functoin

Each Cell has one fxnl copy

LOH of RB1 gene

wt allele

normal function

if only functional copy mutate and no longer works

Loss of Heterozygosity

disease allele

3A

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3B

Subtopic

3C

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Subtopic

mutations of TS genes are dominant

therefor likely to develop a tumour

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

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

Unilateral - when the tumors are present in one eye

Bilateral - when the tumors occur in both eyes

Unifocal - when a single RB tumor is present

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

patients with germline chromosomal deletions of RB1

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

tumours

Doesn't Make Sense

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

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

This Paper is about Testing Survival Gene hypothesis

Floating topic

Non-Heritable RB1-/- Retinoblastoma

Heritable RB1-/- Retinoblastoma

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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.

3D

Subtopic

Reverse Transcription quantitative real time PCR

Western Blot

Floating topic

Floating topic

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