Mitochondrial DNA as a clonal tumor cell marker: gliomatosis cerebri.
The aim of this study was a clonal analysis of gliomatosis cerebri (GC), a rare disease characterized by diffuse, extensively infiltrating glial tumors of the central nervous system. Two females of the series were not informative in assays for X-chromosomal inactivation, and a polycytosine tract of the mitochondrial DNA (mtDNA) was tested as a clonal marker. Following fluorescent PCR, a fraction of human individuals shows several electrophoretic bands in normal tissues, some of which can be lost in corresponding glial tumors. Two male patients of our series fulfilled this prerequisite and were thus informative. In patient 1, four tumor samples from the left temporal and occipital cortex, histologically corresponding to WHO grades III and IV, showed an identical loss of bands, which was not observed in tumor-free brain and in tumors from the left cerebellum, from fornix and corpus callosum, and from the right occipital cortex, corresponding to WHO grades III and IV. Since this patient exhibited a TP53 mutation in exon 7, we sequenced this exon in all tissue samples of this individual. The mutation was found selectively in the tumor samples with a loss of mtDNA bands. In patient 2, all tumors (histologically corresponding to WHO grade II) from putamen, thalamus, midbrain and right parietal cortex exhibited an identical loss of bands in the mtDNA analysis. Taken together, these results support that even distant tumors in a patient with GC can share a common clonal origin. They demonstrate the extraordinary mobility and infiltrative power of these tumor cells.
Kirches
E
E
Department of Neuropathology, Otto-von-Guericke-University, Magdeburg, Germany. elmark.kirches@medizin.uni-magdeburg.de
Mawrin
C
C
Schneider-Stock
R
R
Krause
G
G
Scherlach
C
C
Dietzmann
K
K
D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D041321:Chromosomes, Human, X / Q000235:genetics; D002999:Clone Cells / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018302:Neoplasms, Neuroepithelial / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D014408:Biomarkers, Tumor; D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53