Identificador persistente para citar o vincular este elemento: http://hdl.handle.net/10553/51083
Título: The hMSH2(M688R) lynch syndrome mutation may function as a dominant negative
Autores/as: Martín-López, Juana V.
Barrios, Ysamar
Medina-arana, Vicente
Andújar, Miguel 
Lee, Sanghee
Gu, Liya
Li, Guo Min
Rüschoff, Josef
Salido, Eduardo
Fishel, Richard
Clasificación UNESCO: 32 Ciencias médicas
320713 Oncología
Palabras clave: Mutation
Polymorphism
Central nervous system neoplasms
Adenosine triphosphatases
Hereditary nonpolyposis colorectal neoplasms, et al.
Fecha de publicación: 2012
Publicación seriada: Carcinogenesis 
Resumen: The hMSH2(M688R) mismatch repair (MMR) gene mutation has been found in five large families from Tenerife, Spain, suggesting it is a Lynch syndrome or hereditary non-polyposis colorectal cancer (LS/HNPCC) founder mutation. In addition to classical LS/HNPCC tumors, these families present with a high incidence of central nervous system (CNS) tumors normally associated with Turcot or constitutional mismatch repair deficiency (CMMR-D) syndromes. Turcot and CMMR-D mutations may be biallelic, knocking out both copies of the MMR gene. The hMSH2(M688R) mutation is located in the ATP hydrolysis (ATPase) domain. We show that the hMSH2(M688R)–hMSH6 heterodimer binds to mismatched nucleotides but lacks normal ATP functions and inhibits MMR in vitro when mixed with the wild-type (WT) heterodimer. Another alteration that has been associated with LS/HNPCC, hMSH2(M688I)–hMSH6, displays no identifiable differences with the WT heterodimer. Interestingly, some extracolonic tumors from hMSH2(M688R) carriers may express hMSH2–hMSH6, yet display microsatellite instability (MSI). The functional analysis along with variability in tumor expression and the high incidence of CNS tumors suggests that hMSH2(M688R) may act as a dominant negative in some tissues, while the hMSH2(M688I ) is most likely a benign polymorphism.
URI: http://hdl.handle.net/10553/51083
ISSN: 0143-3334
DOI: 10.1093/carcin/bgs199
Fuente: Carcinogenesis[ISSN 0143-3334],v. 33(9), p. 1647-1654 (Septiembre 2012)
Colección:Artículos
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