Dataset Information

Positron emission tomography in asymptomatic gene carriers of Machado-Joseph disease.

ABSTRACT: The metabolic changes in the brain of symptomatic subjects affected with Machado-Joseph disease have been previously documented using PET with fluorine-18-fluorodeoxyglucose (FDG). The aim of this study was to evaluate these changes in asymptomatic Machado-Joseph disease gene carriers.Seven asymptomatic Machado-Joseph disease gene carriers, identified using a molecular test, and 10 normal control subjects were recruited for PET studies using FDG. Regional uptake ratios of FDG were calculated from the radioactivity of the cerebellar hemispheres, brainstem, and the temporal, parietal and occipital cortices, divided by the activity in the thalamus.In comparison with data obtained from normal control subjects, there was significantly decreased FDG utilisation in the cerebellar hemispheres, brainstem, and occipital cortex, and increased FDG metabolism in the parietal and temporal cortices of asymptomatic Machado-Joseph disease gene carriers, suggesting preclinical disease activity. Discriminant analysis of regional FDG uptake correctly classified genetic status (Machado-Joseph disease mutation carriers v mutation negative subjects) in 25 of 25 subjects (100% sensitivity and 100% specificity), and clinical status (asymptomatic mutation carriers v symptomatic patients) in 14 of 15 subjects (100% sensitivity and 85.7% specificity).Subclinical changes of FDG consumption, as measured by noninvasive PET, can act as an objective marker of preclinical disease activity in Machado-Joseph disease.

SUBMITTER: Soong BW

PROVIDER: S-EPMC2170028 | biostudies-other | 1998 Apr

REPOSITORIES: biostudies-other

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Positron emission tomography in asymptomatic gene carriers of Machado-Joseph disease.

Soong B W BW Liu R S RS

Journal of neurology, neurosurgery, and psychiatry 19980401 4

<h4>Objectives</h4>The metabolic changes in the brain of symptomatic subjects affected with Machado-Joseph disease have been previously documented using PET with fluorine-18-fluorodeoxyglucose (FDG). The aim of this study was to evaluate these changes in asymptomatic Machado-Joseph disease gene carriers.<h4>Methods</h4>Seven asymptomatic Machado-Joseph disease gene carriers, identified using a molecular test, and 10 normal control subjects were recruited for PET studies using FDG. Regional uptak ...[more]

PMID: 9576542

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Project description:Fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is widely used as positron-emission-tomography (PET) radiotracer for the detection and staging of human cancer. Tumor uptake of FDG varies substantially between different cancer types and between patients with the same tumor type. The molecular basis for this heterogeneity is unknown. Using cancer cell lines and primary human tumors of distinct histologic origins, we here show that increased FDG uptake is universally associated with coordinate upregulation of genes within the glycolysis, pentose-phosphate, and other related metabolic pathways. In primary human breast cancers, this FDG signature shows significant overlap with established breast cancer signatures for the “basal-like” disease subtype and “poor prognosis”. FDG high breast cancer showed significantly more gene copy number alterations genome wide than FDG low cancers. About 50 % of primary breast cancers with high FDG uptake and FDG gene expression signature show DNA copy gain encompassing the c-myc gene locus and express gene sets regulated by the transcription factor MYC. Our data shows that FDG-PET marks a distinct subset of “basal-like” human breast cancer which is characterized by MYC and prognostically unfavorable gene expression signatures, suggesting that FDG-PET imaging may be useful to risk-stratify patients with locally advanced breast cancer. Our general strategy to identify molecular determinants of FDG-retention through a genome-wide approach consisted of FDG uptake measurements in cancer cell lines and primary human tumors, the selection of samples with particularly high versus low FDG-retention, and subsequent pathway-based analysis of RNA expression data collected from these samples. Cell line RNA was extracted from a 10 cm plate seeded simultaneously and at the same density as the wells for FDG-uptake assays. For primary human tumor samples, RNA was extracted from macrodissected frozen tumor tissue. All cell line RNA samples and the astrocytoma RNA aliquots were hybridized to Affymetrix U133 Plus 2.0 arrays. All primary breast cancer RNA samples were hybridized to Affymetrix U133A arrays.

Dataset Information

Positron emission tomography in asymptomatic gene carriers of Machado-Joseph disease.

Publications

Positron emission tomography in asymptomatic gene carriers of Machado-Joseph disease.

Similar Datasets

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