AIM: Microsatellite instability (MSI) has been proposed as a possible mechanism in the development of cancer. The aim of the current study was to determine whether MSI is involved in the pathogenesis of paediatric malignant astrocytomas. METHODS: We screened a cohort of 126 high-grade astrocytoma samples for MSI using a sensitive and precise method of DNA analysis including a panel of five mononucleotide repeats, in combination with immunohistochemistry for DNA mismatch repair (MMR) proteins. RESULTS: We identified low level of MSI (MSI-L) in four of 126 (3.2%) paediatric malignant astrocytic tumours. To analyse the molecular profile associated with MSI-L positive tumours, we performed immunohistochemistry for protein expression of hMSH6 and p53 as well as mutational analysis of the K-ras gene. In MSI-L paediatric malignant astrocytic tumours we detected retained nuclear expression of hMSH6 protein and strong nuclear accumulation of p53 protein indicating possible mutations of TP53. There was no correlation between K-ras mutational status and frequency of MSI in this patient population. CONCLUSION: Our results suggest that the MSI-L phenotype is associated with p53 accumulation and/or mutations. However, this represents only a small subgroup of paediatric gliomas with possible distinct biological features, and the deficiencies of DNA MMR genes do not play a main role in the tumourigenesis of the majority of paediatric malignant astrocytomas.
AIM: Microsatellite instability (MSI) has been proposed as a possible mechanism in the development of cancer. The aim of the current study was to determine whether MSI is involved in the pathogenesis of paediatric malignant astrocytomas. METHODS: We screened a cohort of 126 high-grade astrocytoma samples for MSI using a sensitive and precise method of DNA analysis including a panel of five mononucleotide repeats, in combination with immunohistochemistry for DNA mismatch repair (MMR) proteins. RESULTS: We identified low level of MSI (MSI-L) in four of 126 (3.2%) paediatric malignant astrocytic tumours. To analyse the molecular profile associated with MSI-L positive tumours, we performed immunohistochemistry for protein expression of hMSH6 and p53 as well as mutational analysis of the K-ras gene. In MSI-L paediatric malignant astrocytic tumours we detected retained nuclear expression of hMSH6 protein and strong nuclear accumulation of p53 protein indicating possible mutations of TP53. There was no correlation between K-ras mutational status and frequency of MSI in this patient population. CONCLUSION: Our results suggest that the MSI-L phenotype is associated with p53 accumulation and/or mutations. However, this represents only a small subgroup of paediatric gliomas with possible distinct biological features, and the deficiencies of DNA MMR genes do not play a main role in the tumourigenesis of the majority of paediatric malignant astrocytomas.
Authors: A O von Bueren; M D Bacolod; C Hagel; K Heinimann; A Fedier; U Kordes; T Pietsch; J Koster; M A Grotzer; H S Friedman; G Marra; M Kool; S Rutkowski Journal: Br J Cancer Date: 2012-09-13 Impact factor: 7.640
Authors: Marta Viana-Pereira; Alicia Lee; Sergey Popov; Dorine A Bax; Safa Al-Sarraj; Leslie R Bridges; João N Stávale; Darren Hargrave; Chris Jones; Rui M Reis Journal: PLoS One Date: 2011-05-26 Impact factor: 3.240