Evaluation of well-differentiated/de-differentiated liposarcomas by high-resolution oligonucleotide array-based comparative genomic hybridization.

Well-differentiated/de-differentiated liposarcomas (WDLS/DDLS) encompass an intriguing disease model in which a temporal intersection occurs between the malignant transformation of mesenchymal cells and the process of adipogenesis. Deciphering the molecular events that trigger and are characteristic of the intersection of these oncogenic and normal processes is critical to affect the often morbid and lethal consequences of malignant tumors of fat. High-resolution genome-wide oligonucleotide array-based comparative genomic hybridization (aCGH) with matched gene expression analyses was performed on seven lipomas, one hibernoma, and 38 WD and DDLS to define and compare the genomic events associated with these tumors.

PTEN dosage is essential for neurofibroma development and malignant transformation.

Patients with neurofibromatosis type 1 (NF1) carry approximately a 10% lifetime risk of developing a malignant peripheral nerve sheath tumor (MPNST). Although the molecular mechanisms underlying NF1 to MPNST malignant transformation remain unclear, alterations of both the RAS/RAF/MAPK and PI3K/AKT/mTOR signaling pathways have been implicated. In a series of genetically engineered murine models, we perturbed RAS/RAF/MAPK or/and PTEN/PI3K/AKT pathway, individually or simultaneously, via conditional activation of K-ras oncogene or deletion of Nf1 or Pten tumor suppressor genes.

Pten deletion in adult neural stem/progenitor cells enhances constitutive neurogenesis.

Here we show that conditional deletion of Pten in a subpopulation of adult neural stem cells in the subependymal zone (SEZ) leads to persistently enhanced neural stem cell self-renewal without sign of exhaustion. These Pten null SEZ-born neural stem cells and progenies can follow the endogenous migration, differentiation, and integration pathways and contribute to constitutive neurogenesis in the olfactory bulb. As a result, Pten deleted animals have increased olfactory bulb mass and enhanced olfactory function.