Human BCAS3 Expression in Embryonic Stem Cells and Vascular Precursors Suggests a Role in Human Embryogenesis and Tumor Angiogenesis

Cancer is often associated with multiple and progressive genetic alterations in genes that are important for normal development. BCAS3 (Breast Cancer Amplified Sequence 3) is a gene of unknown function on human chromosome 17q23, a region associated with breakpoints of several neoplasms. The normal expression pattern of BCAS3 has not been studied, though it is implicated in breast cancer progression. Rudhira, a murine WD40 domain protein that is 98% identical to BCAS3 is expressed in embryonic stem (ES) cells, erythropoiesis and angiogenesis. This suggests that BCAS3 expression also may not be restricted to mammary tissue and may have important roles in other normal as well as malignant tissues. We show that BCAS3 is also expressed in human ES cells and during their differentiation into blood vascular precursors. We find that BCAS3 is aberrantly expressed in malignant human brain lesions. In glioblastoma, hemangiopericytoma and brain abscess we note high levels of BCAS3 expression in tumor cells and some blood vessels. BCAS3 may be associated with multiple cancerous and rapidly proliferating cells and hence the expression, function and regulation of this gene merits further investigation. We suggest that BCAS3 is mis-expressed in brain tumors and could serve as a human ES cell and tumor marker

Detection of GD2-positive cells in bone marrow samples and survival of patients with localised neuroblastoma

The impact of bone marrow (BM) GD2-positive cells on survival has been evaluated in 145 Italian children with localised neuroblastoma (NB) evaluated at diagnosis by anti-GD2 immunocytochemistry. Nineteen of these (13.1%) were found to be BM GD2-positive, with the number of positive cells ranging between 1 and 155 out of 1 × 106 total cells analysed. Seven/19 (38.8%) GD2-positive vs 12/126 (9.5%) GD2-negative patients relapsed. The 5-year event-free survival (EFS) and overall survival of the GD2-positive patients was significantly worse than that of the GD2-negative ones (62.2 vs 89.9%, P<0.001; and 74.9 vs 95.9%, P=0.005, respectively). GD2 positivity was not associated to other known risk factors, and in particular to Myc-N amplification and 1p deletion. Among Myc-N-negative patients, the EFS of those negative for both GD2 and 1p deletion was significantly better than in children positive for either one of these two markers (EFS=96.9 vs 66.0%, P<0.001). In conclusion, GD2 positivity may represent a prognostic marker for patients with non-metastatic NB without Myc-N amplification, and its combination with genetic alterations might help identifying patients that require a more careful follow-up

Ritual and transition: The Truth Commission in Alexandra Township, South Africa 1996

African Studies Seminar series. Paper presented 11 May, 1998The South African Truth Commission has three Committees — one on Human Rights Violations, one on Amnesty and one on Reparation and Rehabilitation. Together they are, in the words of the Commission itself, designed to 'reveal the truth about the political conflicts of the past.1 Their ultimate aim is to develop a 'culture of human rights in our country, so that the suffering and injustices of the past never occur again.'. This paper examines the operation of one of these committees, that on Human Rights Violations in Alexandra township. Alex was the home of many of South Africa's political leaders during the struggle against apartheid. It was a place where intense political and social conflicts occurred throughout the period covered by the Commission (1960 - 1993), peaking in a strikingly focused period of rebellion in the mid 1980s. The Truth Commission has taken thousands of statements from victims of apartheid, hundreds of them residents in the townships of Johannesburg. People were asked to come forward if they or their kin had been killed, abducted, tortured or severely ill treated for political reasons. The commission defined such experiences as gross human rights violations. It undertook to investigate them through its Investigative Unit. It aimed to find out who was responsible for these, how and why they happened; and to hold public hearings. The Committee on Reparation and Rehabilitation would receive the information thus derived, consult with 'communities' and make policy recommendations to the President for appropriate reparation to victims. This paper is concerned with only one of these activities, the holding of hearings throughout the country, at which victims could speak out and be heard and seen by the public of their own communities. Many hearings were recorded for television, but usually only brief extracts were shown. The paper explores one of these hearings in more detail. Of the many who had been victims of apartheid in the township of Alexandra, 22 were invited to present their testimonies concerning resistance in the township between the 1960s and late 1980s. I attended two of the three days during which the commission sat in Alexandra and heard these 22 testimonies. Listening to the testimonies presented, many of them by people not well known outside Alexandra itself — the classic subjects of oral histories- led me to realise that the public hearings were unique. They involved entirely different processes from the taking of oral histories of the period and they were quite unlike court cases as well. The commission has chosen to use the method of ritual rather than that of law to carry out its purpose. This paper explores this procedure, using the case of one relatively small but extremely significant part of the country as its lens

Unequivocal delineation of clinicogenetic subgroups and development of a new model for improved outcome prediction in neuroblastoma

PURPOSE: Neuroblastoma is a genetically heterogeneous pediatric tumor with a remarkably variable clinical behavior ranging from widely disseminated disease to spontaneous regression. In this study, we aimed for comprehensive genetic subgroup discovery and assessment of independent prognostic markers based on genome-wide aberrations detected by comparative genomic hybridization (CGH). MATERIALS AND METHODS: Published CGH data from 231 primary untreated neuroblastomas were converted to a digitized format suitable for global data mining, subgroup discovery, and multivariate survival analyses. RESULTS: In contrast to previous reports, which included only a few genetic parameters, we present here for the first time a strategy that allows unbiased evaluation of all genetic imbalances detected by CGH. The presented approach firmly established the existence of three different clinicogenetic subgroups and indicated that chromosome 17 status and tumor stage were the only independent significant predictors for patient outcome. Important new findings were: (1) a normal chromosome 17 status as a delineator of a subgroup of presumed favorable-stage tumors with highly increased risk; (2) the recognition of a survivor signature conferring 100% 5-year survival for stage 1, 2, and 4S tumors presenting with whole chromosome 17 gain; and (3) the identification of 3p deletion as a hallmark of older age at diagnosis. CONCLUSION: We propose a new regression model for improved patient outcome prediction, incorporating tumor stage, chromosome 17, and amplification/deletion status. These findings may prove highly valuable with respect to more reliable risk assessment, evaluation of clinical results, and optimization of current treatment protocols