Genome-wide reduction in 5-methylcytosine is an epigenetic hallmark of human tumorigenesis. Experimentally induced hypomethylation in mice promotes genomic instability and is sufficient to initiate tumorigenesis. Here, we report that global hypomethylation is common in primary human glioblastomas [glioblastoma multiforme (GBM)] and can affect up to an estimated 10 million CpG dinucleotides per ...

Frequent early development of systemic metastasis leads to unfavourable clinical prognosis of non-small cell lung cancer (NSCLC). Although brain metastasis (BM) contributes significantly to morbidity and mortality of NSCLC, relevant driver mechanisms are largely unknown. To elucidate genetic alterations associated with early BM of NSCLC, we retros...

BACKGROUND Autism spectrum disorders (ASDs) are a group of highly heritable neurodevelopmental disorders which are characteristically comprised of impairments in social interaction, communication and restricted interests/behaviours. Several cell adhesion transmembrane leucine-rich repeat (LRR) proteins are highly expressed in the nervous system and are thought to be key regulators of its develo...

Almost 70% of urinary bladder neoplasms present as low-grade papillary noninvasive tumors (stage pTa). To determine which genomic alterations can occur in pTa tumors of different grades and to evaluate the prognostic significance of chromosomal imbalances, we analyzed 113 pTa tumors (40 grade 1, 55 grade 2, 18 grade 3) by comparative genomic hybridization. pTaG1 (1.9 +/- 2.0) and pTaG2 (3.1 +/-...

BACKGROUND Medulloblastomas are the most common primary malignant childhood intracranial neoplasms. Patients are currently sorted into three risk groups based on clinical criteria: standard, poor, and infant (<18 months old). We hypothesized that genetic copy number aberrations (CNA) predict prognosis and would provide improved criteria for predicting outcome. METHODS DNA from 35 medulloblast...

OBJECTIVES Genetic causes of sporadic and familial renal oncocytomas are not known. We analyzed these tumors genetically in order to detect tumor-specific chromosome alterations. METHODS DNA from 26 sporadic and 31 familial renal oncocytomas were screened by comparative genomic hybridization according to standard protocols including degenerate oligonucleotide-primed PCR. RESULTS Chromosome ...

PURPOSE Although the genetic alterations in glioblastoma have been well characterized, reports regarding their prognostic effects have been inconsistent. EXPERIMENTAL DESIGN In this series of 140 consecutive cases of glioblastoma treated at a single center, we analyzed the frequency, age dependency and prognostic effects of TP53 mutation, CDKN2A/p16 deletion, EGFR amplification, as well as lo...

Molecular genetics and biology have been having significant influence on the practice of neuro-oncology in recent years, with oligodendrogliomas being the most prominent example. The majority of oligodendrogliomas show remarkable sensitivity to chemotherapy, and the finding that the loss of chromosome 1p was tightly associated with the response opened a new era in which the treatment can be tai...

The high mutation rate in advanced brain tumors, recent functional studies, and the high frequency of mutations in prostate metastases all strongly suggest that PTEN/MMAC1 alterations are involved in the formation of metastases. We searched for genetic alterations in the PTEN/MMAC1 gene in 56 consecutive brain metastases from various primary tumors by loss of heterozygosity (LOH), direct sequen...

Excess O-glycosylation of proteins by O-linked beta-N-acetylglucosamine (O-GlcNAc) may be involved in the pathogenesis of type 2 diabetes. The enzyme O-GlcNAc-selective N-acetyl-beta-d glucosaminidase (O-GlcNAcase) encoded by MGEA5 on 10q24.1-q24.3 reverses this modification by catalyzing the removal of O-GlcNAc. We have previously reported the linkage of type 2 diabetes and age at diabetes ons...