Dedifferentiated liposarcoma of the pleura mimicking a malignant solitary fibrous tumor and associated with dedifferentiated liposarcoma of the mediastinum: usefulness of cytogenetic and molecular genetic analyses.

Dedifferentiated liposarcoma of the pleura is an extremely rare malignancy mimicking a variety of tumors, such as other sarcomas, mesothelioma, and malignant solitary fibrous tumor of the pleura. Liposarcoma of the pleura can be combined with mediastinal involvement, and in most cases it may be impossible to be certain where the primary tumor originated. In this report, we describe a very rare occurence of a dedifferentiated liposarcoma of the pleura in a 76-year-old woman associated with a distinct second dedifferentiated liposarcoma of the mediastinum.

JUN oncogene amplification and overexpression block adipocytic differentiation in highly aggressive sarcomas.

The human oncogene JUN encodes a component of the AP-1 complex and is consequently involved in a wide range of pivotal cellular processes, including cell proliferation, transformation, and apoptosis. Nevertheless, despite extensive analyses of its functions, it has never been directly involved in a human cancer. We demonstrate here that it is highly amplified and overexpressed in undifferentiated and aggressive human sarcomas, which are blocked at an early step of adipocyte differentiation.

Ovarian dysgerminoma and Apert syndrome.

Apert syndrome is an autosomal dominant disorder that results from gain-of-function mutations in the FGFR2 gene. FGFR2 also has been shown to be amplified in stomach and breast cancers. We report the case of a 13-year-old female with Apert syndrome who developed an ovarian dysgerminoma.

VAMP: visualization and analysis of array-CGH, transcriptome and other molecular profiles.

Motivation: Microarray-based CGH (Comparative Genomic Hybridization), transcriptome arrays and other large-scale genomic technologies are now routinely used to generate a vast amount of genomic profiles. Exploratory analysis of this data is crucial in helping to understand the data and to help form biological hypotheses. This step requires visualization of the data in a meaningful way to visualize the results and to perform first level analyses.

Spatial normalization of array-CGH data.

Background: Array-based comparative genomic hybridization (array-CGH) is a recently developed technique for analyzing changes in DNA copy number. As in all microarray analyses, normalization is required to correct for experimental artifacts while preserving the true biological signal. We investigated various sources of systematic variation in array-CGH data and identified two distinct types of spatial effect of no biological relevance as the predominant experimental artifacts: continuous spatial gradients and local spatial bias.

Two types of chromosome 1p losses with opposite significance in gliomas.

Deletion of the short arm of chromosome 1 (1p) is considered a favorable prognostic factor in glial tumors. High-density array-comparative genomic hybridization analysis of 108 gliomas shows two distinct types of 1p deletions. Complete hemizygous losses of 1p, which are tightly associated with 19q loss and oligodendroglial phenotype, and partial 1p deletions mainly observed in astrocytic tumors and not associated with 19q loss.

Mononucleotide repeats BAT-26 and BAT-25 accurately detect MSI-H tumors and predict tumor content: implications for population screening.

Tumors with a defective DNA mismatch repair system (MSI-H tumors) have distinct molecular and clinicopathologic profiles compared with mismatch repair-proficient tumors and are associated with a relatively favorable prognosis. There is evidence to suggest that colorectal cancer patients with MSI-H tumors respond differently to adjuvant chemotherapy. Determination of MSI status also has clinical application for assisting in the diagnosis of suspected hereditary nonpolyposis colorectal cancer cases.

The mutator pathway is a feature of immunodeficiency-related lymphomas.

The mutator phenotype caused by defects in the mismatch repair system is observed in a subset of solid neoplasms characterized by widespread microsatellite instability-high (MSI-H). It is known to be very rare in non-Hodgkin lymphomas (NHL), whereas mutator NHL is the most frequent tumor subtype in mismatch repair-deficient mice. By screening a series of 603 human NHL with specific markers of the mutator phenotype, we found here 12 MSI-H cases (12/603, 2%).

Activated BRAF targets proximal colon tumors with mismatch repair deficiency and MLH1 inactivation.

BRAF, a serine/threonine kinase of the RAF family, is a downstream transducer of the RAS-regulated MAPK pathway and signals upstream of MEK1/2 kinases. Recently, activating mutations within BRAF have been reported in a high percentage of melanomas and colorectal carcinomas and shown to have oncogenic capabilities. Further, their association to mismatch-repair-deficient tumors has suggested the involvement of the RAS/RAF pathway in the tumorigenesis of microsatellite-unstable colon cancers, and that RAS and RAF mutations are alternative genetic events.

BRAF mutations characterize colon but not gastric cancer with mismatch repair deficiency.

Genes from the RAF family are Ras-regulated kinases involved in growth cellular responses. Recently, a V599E hotspot mutation within the BRAF gene was reported in a high percentage of colorectal tumors and significantly associated to defective mismatch repair (MMR). Additionally, BRAF mutations were described only in K-Ras-negative colon carcinomas, suggesting that BRAF/K-Ras activating mutations might be alternative genetic events in colon cancer.