Skip Navigation


Human Molecular Genetics Advance Access originally published online on November 24, 2004
Human Molecular Genetics 2005 14(2):235-239; doi:10.1093/hmg/ddi021
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
14/2/235    most recent
ddi021v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (12)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Alazzouzi, H.
Right arrow Articles by Schwartz, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Alazzouzi, H.
Right arrow Articles by Schwartz, S., Jr
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, Vol. 14, No. 2 © Oxford University Press 2005; all rights reserved

Low levels of microsatellite instability characterize MLH1 and MSH2 HNPCC carriers before tumor diagnosis

Hafid Alazzouzi1, Enric Domingo1, Sara González2, Ignacio Blanco3, Manel Armengol1, Eloi Espín1, Alberto Plaja1, Simó Schwartz1, Gabriel Capella2 and Simó Schwartz, Jr1,*

1Molecular Oncology and Aging Research, Centre d'Investigacions en Bioquímica i Biologia Molecular (CIBBIM), Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron 119-129, Barcelona 08035, Spain, 2Translational Research Unit and 3Genetic Counseling Unit, Institut Català d'Oncologia, Gran Via s/n Km 2.7, 08907 L'Hospitalet, Spain

* To whom correspondence should be addressed. Tel: +34 934894060; Fax: +34 934894040; Email: sschwartz{at}vhebron.net

Received July 28, 2004; Revised September 22, 2004; Accepted November 9, 2004

Microsatellite instability (MSI) characterizes tumors arising in patients with hereditary non-polyposis colorectal cancer (HNPCC) syndrome. HNPCC is a hereditary autosomal dominant disease caused by germline mutations in genes from the DNA (MMR) mismatch repair system. In these tumors, the loss of MMR compromises the genome integrity, allowing the progressive accumulation of mutations and the establishment of a mutator phenotype in a recessive manner. It is not clear, however, whether MSI can be detected in HNPCC carriers before tumor diagnosis. The aim of this study was to evaluate the presence of genetic instability in MMR gene carriers in peripheral blood lymphocytes of carriers and non-carriers members of two HNPCC families harboring a germline MLH1 and MSH2 mutation, respectively. An extensive analysis of the allelic distribution of single molecules of the polyA tract bat26 was performed using a highly sensitive PCR-cloning approach. In non-carriers, the allelic distribution of single bat26 molecules followed a gaussian distribution with no bat26 alleles shorter than (A)21. All mutation carriers showed unstable alleles [(A)20 or shorter] with an overall frequency of 5.6% (102/1814). We therefore suggest that low levels of genomic instability characterize MMR mutation carriers. These observations suggest that somatic mutations accumulate well before tumor diagnosis. Even though it is not clear whether this is due to the presence of a small percentage of cells with lost MMR or due to MMR haploinsufficiency, detection of these short unstable alleles might help in the identification of asymptomatic carriers belonging to families with no detectable MMR gene mutations.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 CarcinogenesisHome page
A.H.S. Gylling, T.T. Nieminen, W.M. Abdel-Rahman, K. Nuorva, M. Juhola, E.I. Joensuu, H.J. Jarvinen, J.-P. Mecklin, M. Aarnio, and P.T. Peltomaki
Differential cancer predisposition in Lynch syndrome: insights from molecular analysis of brain and urinary tract tumors
Carcinogenesis, July 1, 2008; 29(7): 1351 - 1359.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
A. Tsirigos and I. Rigoutsos
Human and mouse introns are linked to the same processes and functions through each genome's most frequent non-conserved motifs
Nucleic Acids Res., June 1, 2008; 36(10): 3484 - 3493.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
E. Avdievich, C. Reiss, S. J. Scherer, Y. Zhang, S. M. Maier, B. Jin, H. Hou Jr, A. Rosenwald, H. Riedmiller, R. Kucherlapati, et al.
Distinct effects of the recurrent Mlh1G67R mutation on MMR functions, cancer, and meiosis
PNAS, March 18, 2008; 105(11): 4247 - 4252.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
S. L. Cossio, P. Ashton-Prolla, M.-C. Bortolini, R. S. Coura, R. Giugliani, and J. C. Prolla
Microsatellite Instability Testing in Genetically Heterogeneous Populations
J. Clin. Oncol., March 1, 2007; 25(7): 913 - 914.
[Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
E. C. Chao and S. M. Lipkin
Molecular models for the tissue specificity of DNA mismatch repair-deficient carcinogenesis
Nucleic Acids Res., February 6, 2006; 34(3): 840 - 852.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.