2011年11月15日星期二

Introduction to Cancer Genetics

most cancers is a basic time period, describing a gaggle of numerousillnesses. for the reason thatse illnesses are other, it isn't the same asly that a common remedy for cancer will evolve. every form of cancer wishes its own remedy software.

Tlisted below are two not unusual correctties for every form of cancer:

1. extraordinary prolifestylesration (so known as neoplasia, that leads toa neoplasm construction)

2. Invasive ability. correctty that sepacharges benign tumors from cancer.

Cancer cellular telephones invade other areas via commuteling in the course of the circulatory device or lymphatic device. This procedure is named metastasis, during which illness is unfold from one organ to some other non-adjoining organ.

Cancers can be categoryified consistent with cell type.

1.Leunited kingdomemia and Lymphoma

2.Carcinoma

three.Sarcoma

four .cancer

5.Retinobfinaloma, Neurobultimateoma, Gliobultimateoma

(1: bbathroom lood-borne cancers, 2-5: casttumors)

Cancer is a gewebic illness and also might be observed as a distcityce within the cell cycle legislation device. you'll inherit a predisposit downion for cancer, however for the illness to damage out extrasomatic mutations are required. those mutations aupward push from:

1. settingal mutagens (bodily or chemical sellers that fluctuate DNA)

2. Imbest possibleions all through DNa duplicateing and service (so referred to as spontaneous mutations).

Tlisted here are two how one can categorize mutated genes in keeping with serve as:

1.serve as in a cancer cell

- Genes which were turn ond or over specific ed = oncogenes (one mutated allele is sufficient)

- Genes which have been inturn ond:

1.Tumor suppressor genes.

each alleles wish to be mutated. E.g. RB1 and pfifty three

2. DNA-misfit restore genes

each alleles want to be mutated.

2.serve as in customary cell:

- Genes that during an instant keep an eye on proliftechnologytion (keep an eye onling cell start price or dconsumeh fee) = Gatekeepers

- Genes that keep watch over the velotownof mutation = Caretakers

Mutation in some genes at all times leads to the similar form of cancer, inrely ent of what sort of mutation or the place it has aupward thrustn (e.g.WT1). Mutations in other genes result in numeroussorts of cancer (e.g. pfifty three).

Neoplasms have geinternet ic instability. it isn't transparentif the insttalentis the cause of tumor structureion or only a end result. This instskillcan be divided into 2 top teams:

1.Instskillon the chromosomal stage (CIN)

Mutation in a single allele sufficient. Hypomethylation build uplaystation instability.

2.Insttalenton the nucleotide degree: misguided DNA restore coursemanner s

-Nucleotide Excision restore Instskill(NIN)

-Microsainformite instskill(MIN)

Mutation in each alleles important.

DNA adjustations present in tumors (each malignant and benign):

1.refined regulatconsumeions:

Small depermitions, small insertions and base-pair substitutions.

2.Chromosome quantity amendment(aneuploidy):

acquire and absence of chromosomes (which might possibly result in that each chromosomes are from the similar parent. a scartworkownof 1 chromosome regularly leads to the duplication of the rest chromosome).

an ordinary proosteromena is lack of straightzygosity (LOH), which can result in the inactivation of genes (those genes is also suppressor genes, that supplyprotection to the cell from cancer)

three. Chromosome transregion:

Can be both:

1.stabilityd (even exmodificationof subject material)

2.Unstabilityd (unequivalent examinationendmentof fabric). results infurtheror pass overing genes.

Transregion leads to Malignity:

- Transcription issue genes are transferd (to the neighborhood of excessively energetic promenadeotor/fortif12 months components) and therefore becomeover categoricaled.

- Tyearosine kinase genes are fused without armal genes and translation leads to a chimeric protein with oncogenic correctties = fusion protein (expansionissue receptor or inhintllular sign transducers).

Chromosome transregion in Leunited kingdomemia and Lymphoma:

Transplaces are explicit (no longer random).

- Transcription issue transarea:

A. Aminimizee Lymphobultimateic Leunited kingdomemia and Non-Hodgkin Lymphoma (e.g. MYC)

B. Areducee Myeloid Leunited kingdomemia (e.g. AML1-CBF² advanced )

C. Aminimizee combine ed-Lineage Leunited kingdomemia

- Tyearosine kinase transarea

A. persistent Myeloid Leunited kingdomemia (ABL fusion gene)

B. Aminimizee Lymphobremainingic Leunited kingdomemia (ABL fusion gene)

The Philadelphia chromosome is findd as a marker in analysis and that in apply- up of remedy.

four . Amplification:

defined as over 6 copies of a DNA area (known as the amplicon).

those areas so much ceaselessly code for:

1.Transcriptional issue s (MYC-circle of relatives, e.g. MYCN amplification observed in neurobremainingoma)

2.sign transduction moleules (Ras-circle of relatives)

three.enlargementissue s (EGF, FGF), enlargementissue receptors (EGFR, FGFR)

four .Regulators of the cell cycle.

Over categoricalion of those genes provides cancer a enlargementbenefit.

The amplification can be outdoor the chromosome (double minute chromatin our bodies) or throughout the chromosome.

Amplifications can be used inanalysis and focused gene remedy.

5. Exogenous seriess:

E.g. tumor virmakes use of which turn on both human genes or viral genes that result in the buildup of mutations.

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