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Hypermutability in Carcinogenesis and MSI

Posted: Fri Feb 05, 2016 7:45 am
by D.ap
Johannes mentioned a new term to us , microsatellite instability and I found it interesting to pursue.

http://www.cureasps.org/forum/viewtopic ... t=30#p8996

Hypermutability in Carcinogenesis and MSI


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Abstract

The presence of numerous chromosomal changes and point mutations in tumors is well established. At least some of these changes play a role in the development of the tumors. It has been suggested that the number of these genetic changes requires that tumorigenesis involves an increase in mutation rate. However, the presence of numerous changes can also be accounted for by efficient selection. What is required to settle the issue is some measure of nonselected mutations in tumors. In order to determine whether the tumor suppressor TP53 (coding for the protein p53) is hypermutable at some stage of carcinogenesis, the frequency of silent and multiple mutations in this gene has been examined. Silent mutations make up ~3% of the total recorded but constitute 9.5% of the mutations found in tumors with multiple mutations. Multiple closely linked mutations are also observed. Such multiple mutations suggest the operation of an error-prone replication process in a subclass of cells. The published data indicate that TP53 is hypermutable at some stage of tumor development. It is not yet clear whether TP53 is unique or whether other genes display a similar pattern of silent and multiple mutations
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Alveolar soft part sarcoma: review of nine cases including two cases with unusual histology.
Jong R1, Kandel R, Fornasier V, Bell R, Bedard Y.
Author information

Abstract
AIM:

Alveolar soft part sarcoma is a very rare tumour. Nine cases are reviewed in order to identify new aspects of this tumour.

METHODS AND RESULTS:

The clinical course, histological, immunohistochemical and ultrastructural features of nine cases of alveolar soft part sarcoma were reviewed. Proliferative activity and p53 protein accumulation were assessed immunohistochemically. The patients were aged between 18 and 70 years. In the cases with sufficient follow-up, survival was variable with two patients dying within 5 months and four alive at 4 years. Histologically all tumours had an alveolar component but one case also had a spindle component and another case had a pseudoglandular pattern. Six cases showed desmin immunoreactivity, one was muscle-specific actin positive, two were positive for S100 protein and three were positive for vimentin. MIB-1 immunostaining was seen in up to 35% of cells. Two cases showed p53 protein accumulation.

CONCLUSIONS:

There appeared to be no correlation between short term survival (4 years or less) and clinical presentation, adjuvant treatment, tumour size, histological grade, vascular invasion by tumour, proliferative index, or p53 protein accumulation. Although unusual, spindle cell or pseudoglandular components can be seen in alveolar soft part sarcoma.

PMID: 9522219 [PubMed - indexed for MEDLINE]


http://genetics.org/content/148/4/1619

Microsatellite instability (MSI) is the condition of genetic hypermutability that results from impaired DNA mismatch repair (MMR).

Low Level of Microsatellite Instability by Overexpression of DNA Polymerase

Posted: Sat Feb 06, 2016 6:16 am
by D.ap
Induction of a Low Level of Microsatellite Instability by Overexpression of
DNA Polymerase 1


http://cancerres.aacrjournals.org/conte ... 1.full.pdf

Lung tumors seem to be used in a lot of the articles I've read pertaining to MSI

Also genetics can be a big player with higher MSI?

Not sure I'm on the right track.. :roll:


Love
Debbie