chromosomal instability, aneuploidy and tumorigenesis

carfan

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) m+ v4 [7 Q8 ~5 s8 pRecently, Andrew J. Holland and Don W. Cleveland have published their review on Chromosomal instability, aneuploidy and tumorigenesis in Nature Reviews Molecular Cell Biology 10, 478-487 (July 2009) | doi:10.1038/nrm2718.
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  [' ]0 Z& i  i; H# H, jAndrew Holland currently works as a postdoctoral fellow in the laboratory of Don Cleveland. His major research interests are focused on understanding the processes that ensure the faithful distribution of chromosomes during mitosis and the consequences that chromosome missegregation events have for the cell and the organism.& [! W/ E! H6 L
The correspondent, Don Cleveland is the Chair of Cellular and Molecular Medicine and the head of the laboratory of cell biology in the Ludwig Institute for Cancer Research at the University of California, San Diego, USA. His research team has made several important contributions in deciphering the principles of mitotic spindle assembly and chromosome movement. His laboratory identified centromere protein E (CENP-E) and showed that it is required to power chromosome movement during mitosis and meiosis. Recent efforts have shown that CenpE heterozygous mice develop elevated levels of aneuploidy that act to suppress tumorigenesis in specific genetic contexts and cell types.' R" d% V: @$ ~  J
There address information:' {! {6 v6 j0 \8 h
Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine,. X4 g* \7 U; O4 `2 Z  k/ S
University of California, 9500 Gilman Drive, San Diego, La Jolla, California 92093‑0670, USA.8 Z& A* i8 L8 T
Correspondence to D.W.C. e‑mail: dcleveland@ucsd.edu3 }) R* I/ Y) n3 Y

! D0 o; _+ @& |" N: [9 cCell division must accurately duplicate its genome and faithfully partition the duplicated genome into daughter cells. If failed, the resulting daughters might inherit too many or too few chromosomes, a condition that is known as aneuploidy. Over 100 years ago, the German zoologist Theodor Boveri showed that aneuploidy has a detrimental effect on cell and organism physiology. Drawing on this discovery and , He proposed that an abnormal chromosome constitution might promote cancer with von Hansemann’s observations of abnormal mitotic figures in tumour cells. Today, it is clear that aneuploidy is a common genetic feature of solid human tumours. However, whether aneuploidy is a cause or a consequence of malignant transformation remains hotly debated. Indeed, coupled with numerical changes in whole chromosomes, cancer cells often display structural chromosomal alterations, including deletions, amplifications and translocations.  They reviewed the pathways by which aneuploidy arises and consider the defects that allow frequent chromosome missegregation in cancer cells. They also discussed evidence that suggests a causative role for aneuploidy in the development of tumours and highlight surprising new evidence that shows aneuploidy can suppress tumorigenesis in certain genetic contexts and cell types." }+ k; j  }+ r$ _2 ~
For example, whereas mice that are heterozygous for CenpE exhibit an increase in the rate of spontaneous lung and spleen tumours, these animals show a decreased incidence of liver tumours. moreover, patients with Down’s syndrome have a significant increase in haematological cancers but a reduced incidence of solid tumours.
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Therefore, they hypothesized that the effect of aneuploidy might not be driven by a particular combination of chromosomes per se, but rather by the specific interaction of the karyotype with the various genetic contexts and microenvironments found in different tissues.
1 C0 P, F8 N  H7 Q* [% MThe picture copy form the paper of Beth A.A. Weaver and Don W. Cleveland in Cancer research 2007; 67: (21).November 1, 2007, Aneuploidy: Instigator and Inhibitor of Tumorigenesis.
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: c) K& i1 m+ G3 Q; p3 I, T4 l! SAll the resources come form the "Antican Space", and thanks a lot to the original paper writers Andrew J. Holland and Don W. Cleveland.

carfan

why i can not paste the pic and the pdf paper?) W0 ~# |  E$ F: J6 K
why cut 1 bag while i delete the wrong poster of myself?

饶冠华

full text

饶冠华

2# carfan 6 H& Q$ V! [7 ~& o, A2 W3 z( B# Y+ J

+ e; u5 L6 Z$ x, Z9 ~thank you for the poster~~actually, aneuploidy is much more important in the process of cancer evolution. however, lots of cancer researchers ignore this~~

carfan

4# 饶冠华
, z, ~5 z9 n$ ^: N6 n, ryes, 100 years ago we have found the aneuploidy is very important for tumorigenesis, but look it from the chromosome and DNA damage level, we agree that the damage can induce apoptosis as well the mutations lead to carcinogensis. Aneuploidy is one kind of chromosome abnormality like the other form of "gene or genomic stucture and function error", our unpublished data showed that bulk chromosome instability(CIN) such as some kind of aneuploidy can cause programmed death of cancer cells, just like the DNA damge drugs can induce both cancer cell death and normal cell transformation.
9 X" P7 Q! T+ EThe different effect come from the specific extent of gene damge and the interaction of signalling pathways with the various genetic contexts and microenvironments found in different tissues or cell lines (normal vs cancer).

carfan

the paper of Beth A.A. Weaver and Don W. Cleveland in Cancer research 2007; 67: (21).November 1, 2007, Aneuploidy: Instigator and Inhibitor of Tumorigenesis.

饶冠华

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5# carfan 2 Q& h" R' }/ {* `

- W- N' U0 U, ?I totally agree with you! and I am glad to have such a bosom friend as you in this cancer research field. so your research interest is focused on chromosome abnormality?

carfan

No, we do not focus in CIN, that only one kind of our data to explain the course of carcinogenesis and the death of cancer cells just like apoptosis.

天天快乐

非常感谢全文的提供

wzx6660

谢谢