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Human Genetics

, Volume 102, Issue 2, pp 231–235 | Cite as

Polarity of mutations in tumor-associated microsatellite instability

  • Rosane Sturzeneker
  • Luciana A. Haddad
  • Roberta A. U. Bevilacqua
  • Andrew J. G. Simpson
  • Sérgio D. J. Pena
Original investigation

Abstract

Many factors have been implicated in influencing the rate of microsatellite mutations, including the length and base composition of the repeat motif, number of repeats, base composition of flanking sequences and, perhaps most importantly, degree of perfection of the repeats. The latter is of clinical relevance, since in both spino-cerebellar ataxia and fragile X syndrome, alleles with imperfect repeats appear to be much more stable than perfect ones. As yet, the relative importance of increased replication slippage and decreased mismatch repair efficiency in the preference of mutations to occur within perfect repeats has not been fully determined. D13S308E is an asymmetric trinucleotide repeat microsatellite with the sequence (CAT)3CAC(CAT)CAC(CAT)2CAC(CAT)CAC(CAT) 15 , thus containing two parts: an 11-repeat imperfect portion (underlined above) and a 15-repeat perfect one (bold). We sequenced eight new mutant alleles of D13S308E from three human gastric tumors with instability in this and other microsatellites. In all mutations the size variation occurred exclusively in the perfect part of the microsatellite. These results constitute direct evidence that the molecular basis of microsatellite alterations seen in normal cells is similar to those that occur in human tumors with extensive microsatellite instability. The investigation of mechanisms involved in microsatellite mutations has been handicapped by the fact that they are rare events. The microsatellite instability observed in malignant tumors provides us with a useful general system to study these mechanisms.

Keywords

Flank Sequence Mismatch Repair Base Composition Microsatellite Instability Repeat Motif 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Rosane Sturzeneker
    • 1
  • Luciana A. Haddad
    • 1
  • Roberta A. U. Bevilacqua
    • 2
  • Andrew J. G. Simpson
    • 2
  • Sérgio D. J. Pena
    • 1
  1. 1.Departamento de Bioquímica e Immunologia, Instituto de Ciências Biológicas - U. F. M. G., Caixa Postal 486, Belo Horizonte, MG, 30161–970 Brazil Tel.: +5531-227-3496; Fax: +5531-227-3792 e-mail: spena@dcc.ufmg.brBR
  2. 2.Laboratory of Cancer Genetics, Ludwig Institute for Cancer Reserach, São Paulo, BrazilBR

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