Angela Bentivegna

Verified

Angela verified their affiliation via an institutional email.

Learn more

Verified

Angela verified their affiliation via an institutional email.

Learn more

• Professor
• Professor (Associate) at Università degli Studi di Milano-Bicocca

Background/Objectives: Aneuploidy is a prevalent cancer feature that occurs in many solid tumors. For example, high-grade serous ovarian cancer shows a high level of copy number alterations and genomic rearrangements. This makes genomic variants appealing as diagnostic or prognostic biomarkers, as well as for their easy detection. In this study, we...

When an increased nuchal translucency (>3.00 mm) is observed during the echographic examination of a foetus in the first trimester of pregnancy, an increased risk of chromosomopathy is considered, and the pregnant woman is offered the possibility of an invasive investigation. Here, we focused our attention on prenatal diagnosis issues in cases of f...

The vacuolar proton-translocating ATPase (V-ATPase) is a transmembrane multi-protein complex fundamental in maintaining a normal intracellular pH. In the tumoral contest, its role is crucial since the metabolism underlying carcinogenesis is mainly based on anaerobic glycolytic reactions. Moreover, neoplastic cells use the V-ATPase to extrude chemot...

The vacuolar proton translocating ATPase (V-ATPase) is a transmembrane multi-protein complex fundamental in maintaining a normal intracellular pH. In the tumoral contest, its role is crucial since the metabolism is mainly based on anaerobic glycolytic reactions. Moreover, the neoplastic cells use the V-ATPase to extrude chemotherapy drugs to the ex...

The largest multi-gene family in metazoans is the family of olfactory receptor (OR) genes. Human ORs are organized in clusters over most chromosomes and seem to include >0.1% the human genome. Because 369 out of 856 OR genes are mapped on chromosome 11 (HSA11), we sought to determine whether they mediate structural rearrangements involving this chr...

Special Issue "Exploring the Glioblastoma Complexity: New Perspectives in the Molecular and Imaging Fields"

Special Issue "Exploring the Glioblastoma Complexity: New Perspectives in the Molecular and Imaging Fields"

Complex chromosomal rearrangements are rare events compatible with survival, consisting of an imbalance and/or position effect of one or more genes, that contribute to a range of clinical presentations. The investigation and diagnosis of these cases are often difficult. The interpretation of the pattern of pairing and segregation of these chromosom...

The lack of effective screening and successful treatment contributes to high ovarian cancer mortality, making it the second most common cause of gynecologic cancer death. Development of chemoresistance in up to 75% of patients is the cause of a poor treatment response and reduced survival. Therefore, identifying potential and effective biomarkers f...

Background. Complex chromosomal rearrangements are rare events compatible with survival, consisting in imbalance and/or position effect, which contribute to a range of clinical pictures. The investigation and diagnosis of these cases is often difficult and knowing the methodology followed in similar cases can be very useful for others. The interpre...

Despite the efforts made in recent decades, glioblastoma is still the deadliest primary brain cancer without cure. The potential role in tumour maintenance and progression of the peritumoural brain zone (PBZ), the apparently normal area surrounding the tumour, has emerged. Little is known about this area due to a lack of common definition and due t...

Glioblastoma (GBM) is the most aggressive and invasive primary brain tumor. Current therapies are not curative, and patients' outcomes remain poor with an overall survival of 20.9 months after surgery. The typical growing pattern of GBM develops by infiltrating the surrounding apparent normal brain tissue within which the recurrence is expected to...

Glioblastoma (GBM) is the most aggressive and invasive primary brain tumor. Current therapies are not curative, and patients' outcomes remain poor with an overall survival of 20.9 months after surgery. The typical growing pattern of GBM develops by infiltrating the surrounding apparent normal brain tissue within which the recurrence is expected to...

Glioblastoma (GBM) is the most aggressive tumor of the central nervous system. GBM is a fatal tumor, incurable by conventional therapies. One of the factors underlying tumor recurrence and poor long-term survival is the presence of a cancer stem-like cell population, termed glioma stem cells (GSCs), which is particularly resistant to chemotherapy a...

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with a malignant prognosis. GBM is characterized by high cellular heterogeneity and its progression relies on the interaction with the central nervous system, which ensures the immune-escape and tumor promotion. This interplay induces metabolic, (epi)-genetic and molecular rew...

Purpose Bladder cancer is the most common malignancy of the urinary tract and one of the most prevalent cancers worldwide. It represents a spectrum of diseases, from recurrent non-invasive tumors (NMIBCs) managed chronically, to muscle infiltrating and advanced-stage disease (MIBC) that requires multimodal and invasive treatment. Multiple studies h...

Improvements in microarray-based comparative genomic hybridization technology have allowed for high-resolution detection of genome wide copy number alterations, leading to a better definition of rearrangements and supporting the study of pathogenesis mechanisms. In this study, we focused our attention on chromosome 8p. We report 12 cases of 8p rear...

Glioblastoma (GBM, grade IV glioma) represents the most aggressive brain tumor andpatients with GBM have a poor prognosis. Until now surgical resection followed by radiotherapyand temozolomide (TMZ) treatment represents the standard strategy for GBM. We showed that theimidazobenzoxazin-5-thione MV1035 is able to significantly reduce GBM U87-MG cell...

Glioblastoma is an extremely heterogeneous disease. Treatment failure and tumor recurrence primarily reflect the presence in the tumor core (TC) of the glioma stem cells (GSCs), and secondly the contribution, still to be defined, of the peritumoral brain zone (PBZ). Using the array-CGH platform, we deepened the genomic knowledge about the different...

The study of glioblastoma genomic profiles permits the use of CNAs load to identify patients with poor prognosis and the understanding of the genomic signatures essential for the disease maintenance and the identification of new potential biomarkers.

Recent evidences suggest the involvement of the Vacuolar H+ ATPase (V-ATPase) in the development and/or progression of Glioblastoma Multiforme (GBM). This proton pump could be a valid therapeutic target but more in-depth studies are necessary. The aim of this study is to better define the in vitro effects on Glioma Stem Cell (GSC) primary cultures...

The presence of thousands of repetitive sequences makes the centromere a fragile region subject to breakage. In this study we collected 31 cases of rearrangements of chromosome 18, of which 16 involved an acrocentric chromosome, during genetic screening done in three centers. We noticed a significant enrichment of reciprocal translocations between...

Uterine smooth muscle tumors of uncertain malignant potential (STUMPs) represent a heterogeneous group of tumors that cannot be histologically diagnosed as unequivocally benign or malignant. For this reason, many authors are working to obtain a better definition of diagnostic and prognostic criteria. In this work, we analyzed the genomic and epigen...

Satellited non-acrocentric autosomal chromosomes (ps–qs-chromosomes) are the result of an interchange between sub- or telomeric regions of autosomes and the p arm of acrocentrics. The sequence homology at the rearrangement breakpoints appears to be, among others, the most frequent mechanism generating these variant chromosomes. The unbalanced carri...

Unbalanced X;autosome translocations are a rare occurrence with a wide variability in clinical presentation in which the X chromosome unbalance is usually mitigated by a favorable X inactivation pattern. In most cases, this compensation mechanism is incomplete, and the patients show a syndromic clinical presentation. We report the case of a family...

Glioma stem cells account for glioblastoma relapse and resistance to conventional therapies, and protein kinases, involved in the regulation of the mitotic machinery (i.e., Aurora kinases), have recently emerged as attractive therapeutic targets. In this study, we investigated the effect of Aurora kinases inhibition in five glioma stem cell lines i...

UGT1A1 mutations and psychoses: towards understanding the relationship with unconjugated bilirubin - Angela Bentivegna, Jacopo Santambrogio, Massimo Clerici

Chromosome 16 is one of the most gene-rich chromosomes of our genome, and 10% of its sequence consists of segmental duplications, which give instability and predisposition to rearrangement by the recurrent mechanism of non-allelic homologous recombination. Microarray technologies have allowed for the analysis of copy number variations (CNVs) that c...

Notch signaling is an evolutionarily conserved pathway that regulates important biological processes, such as cell proliferation, apoptosis, migration, self-renewal, and differentiation. In mammals, Notch signaling is composed of four receptors (Notch1–4) and five ligands (Dll1-3–4, Jagged1–2) that mainly contribute to the development and maintenan...

Bruton’s tyrosine-kinase (BTK) is a non-receptor tyrosine kinase recently associated with glioma tumorigenesis and a novel prognostic marker for poor survival in patients with glioma. The p65BTK is a novel BTK isoform involved in different pathways of drug resistance of solid tumors, thus we aimed to investigate the expression and the putative role...

Glioblastoma is the most common malignant brain tumour in adults. The failure of current therapies can be ascribed to glioma stem cells (GSCs), which can rapidly repopulate the tumour following the initial treatment. The study of histone deacetylase inhibitors, such as valproic acid (VPA), is becoming an attractive field in cancer research. However...

Here, we describe the use of complementary techniques applicable to different types of samples to analyze chromosomal alterations in urothelial carcinoma. By a conventional chromosome analysis on fresh biopsies, it is possible to delineate the status of ploidy and rough chromosomal aberrations. The multi-target fluorescence in situ hybridization (F...

Human thyroid cancer derived cell lines are widely used to study the mechanisms involved in thyroid carcinogenesis. However, there is limited availability of non-cross-contaminated cancer cell lines derived from papillary thyroid carcinoma (PTC), and the B-CPAP cell line is one of the few such lines. B-CPAP cells have been genetically and cytogenet...

Supplementary figures and tables.

DNA methylation (DNAm) changes are of increasing relevance to neurodegenerative disorders, including Huntington's disease (HD). We performed genome-wide screening of possible DNAm changes occurring during striatal differentiation in human induced pluripotent stem cells derived from a HD patient (HD-hiPSCs) as cellular model. We identified 240 diffe...

Glioblastoma multiforme (GBM) is a grade IV astrocytoma and the most common form of malignant brain tumor in adults. GBM remains one of the most fatal and least successfully treated solid tumors: current therapies provide a median survival of 12–15 months after diagnosis, due to the high recurrence rate. Glioma Stem Cells (GSCs) are believed to be...

Statistical analysis (p-values, t-test) of the effects of RSV on cell viability. p-values are referred to the specific treatment compared to the respective untreated cells. (DOCX)

Statistical analysis (p-values, t-test) of the effects of RSV on cell motility. p-values are referred to the specific treatment compared to the respective untreated cells. (DOCX)

Glioblastoma (GBM) is the most aggressive tumor of the central nervous system. GBM is a fatal tumor, incurable by conventional therapies. One of the factors underlying tumor recurrence and poor long-term survival is the presence of a cancer stem-like cell population, termed glioma stem cells (GSCs), which is particularly resistant to chemotherapy a...

Bladder cancer represents the ninth most widespread malignancy throughout the world. It is characterized by the presence of two different clinical and prognostic subtypes: non-muscle-invasive bladder cancers (NMIBCs) and muscle-invasive bladder cancers (MIBCs). MIBCs have a poor outcome with a common progression to metastasis. Despite improvements...

Human bone marrow mesenchymal stem cells (hBM-MSCs) are the best characterized multipotent adult stem cells. Their self-renewal capacity, multilineage differentiation potential, and immunomodulatory properties have indicated that they can be used in many clinical therapies. In a previous work we studied the DNA methylation levels of hBM-MSC genomic...

Glioblastoma multiforme (GBM) represents one of the most frequent malignant brain tumors. Current therapies do not provide real solutions to this pathology. Their failure can be ascribed to a cell subpopulation with stem-like properties called glioma stem cells (GSCs). Therefore, new therapeutic strategies GSC-targeted are needed. PPAR γ , a nuclea...

DNA Methylation of Imprinted Genes: We extrapolated a list of 37 genes listed in and included in our MeDIP-CGI-array experiments. The function of each gene was verified by consulting UCSC and listed in Supplemental Table 1.

Glioblastoma multiforme (GBM) is a grade IV astrocytoma and the most common malignant brain tumor. Current therapies provide a median survival of 12-15 months after diagnosis, due to the high recurrence rate. The failure of current therapies may be due to the presence, within the tumor, of cells characterized by enhanced self-renewal capacity, mult...

Background: Glioblastoma multiforme (GBM) is one of the deadliest cancers characterized by very limited sensitivity to chemo- and/or radiotherapy. The presence of GBM stem-like cells in the tumor might be relevant for GBM treatment resistance. Aim: To provide a proof-of-concept of the efficacy of photon activation therapy (PAT) using monochromat...

The existence of two distinct groups of tumors with different clinical characteristic is a remarkable feature of transitional cell carcinomas (TCCs) of the bladder. More than 70% are low-grade (LG) non-infiltrating (NI) cancers at diagnosis, but 60-80% of them recur at least one time and 10-20% progress in stage and grade. On the other hand, about...

Percentages of polymorphic nuclei in untreated, VPA and PTX treated cells.

Differentiation behavior of GSC lines in response to VPA treatment.

Statistical analysis (p-values, t-test) of the effects of VPA and PTX on cell viability (MTT assay). p-values are referred to each specific treated culture compared to respective untreated cells.

(A) The Cooperative Index (CI) for viability assays of VPA plus PTX treatment. CI was calculated to determine the (CI < 1), additive (CI = 1) or antagonistic (CI > 1) effects of the combined treatment. Synergistic CI are indicated in bold.

Top 10 pathways associated to new ‘exclusive’ CNA regions. (DOC)

New ‘exclusive’ CNAs of GSC lines identified through a comparison with literature data. (DOC)

List of CNAs and mosaic level in GBM2 cell line. (DOC)

Panel of GBM2 chromosomal abnormalities identified through FISH analysis. (DOC)

List of CNAs and mosaic level in GliNS2 cell line. (DOC)

Real-time PCR data and promoter methylation of selected genes. (DOC)

Panel of G166 chromosomal abnormalities identified through FISH analysis. (DOC)

List of CNAs and mosaic level in G166 cell line. (DOC)

List of STS markers. (DOC)

Selected representative images of GSC immunofluorescence in standard growth conditions. (DOC)

List of Top 10 pathways influenced by DNA methylation pattern in GSCs. (DOC)

A. Cancer de novo methylated genes: GSC and GBM FFPE tissues vs. foetal NSCs. B. De novo aberrantly methylated genes in GSC lines. (DOC)

Percentages of methylated and unmethylated CGIs in GSCs, foetal NSCs, PBL pool and GBM FFPE tissues, classified in the different functional genomic regions. (DOC)

Quantitative CpG methylation analysis of A) MGMT and B) PDGFB promoters. (DOC)

RT-PCR performed on RNA obtained from GBM2, G166, G179, GliSN2 and GBM7 cells. (DOC)

Glioblastoma multiforme (GBM), the most common and malignant type of glioma, is characterized by a poor prognosis and the lack of an effective treatment, which are due to a small sub-population of cells with stem-like properties, termed glioma stem cells (GSCs). The term "multiforme" describes the histological features of this tumor, that is, the c...

Panel of GliNS2 chromosomal abnormalities identified through FISH analysis. (DOC)

List of CNAs and mosaic level in GBM7 cell line. (DOC)

Methylation status gene promoters associated to GBM pathogenesis. (DOC)

List of CNAs and mosaic level in G179 cell line. (DOC)

Mesenchymal stem cells (MSCs) hold great promise for the treatment of numerous diseases. A major problem for MSC therapeutic use is represented by the very low amount of MSCs which can be isolated from different tissues; thus ex vivo expansion is indispensable. Long-term culture, however, is associated with extensive morphological and functional ch...

Introduction Bone marrow mesenchymal stem cells (BM-MSCs) are multipotent cells that can differentiate into different cell lineages and have emerged as a promising tool for cell-targeted therapies and tissue engineering. Their use in a therapeutic context requires large-scale in vitro expansion, increasing the probability of genetic and epigenetic...

Table S2. GOstat analysis of demethylated and methylated gene promoters in late passages of human bone marrow mesenchymal stem cells (hBM-MSCs).

Figure S1-S4. Figure S1 Left: Fluorescnce in situ hybridization (FISH) analysis with Vysis Williams Region FISH probe ELN (orange 7q11.23)/D7S486, D7S522 (green control probe) on P6 of Donor 4 confirmed the presence of two chromosomes 7. Right: FISH analysis with Poseidon EGFR, Her-1 (7p11; red) and SE7 (D7Z1; green control probe) on P9 of Donor 4...

Table S1. CNVs evidenced by array-CGH in human mesenchymal stem cells (hMSCs) at several passages in culture. The estimated percentage of mosaicism was calculated by using the formula determined by Cheung SW et al. [52].

Background Bladder cancer is the seventh most common cancer worldwide and over 90% are transitional cell carcinoma (TCC). At the first time of diagnosis at least 70% of TCC present as superficial bladder cancer. Because the clinical outcome of superficial bladder tumors is relatively unpredictable, there is a pressing need to identify markers that...

Figure S1. Array-CGH. A: first biopsy. B: third biopsy.

Table S1. Statistically significant ontology classes with p<0.05 from genes included in two CNVs in gain: 3p25.2-p25.1 and 12q23.2. Table S2. Statistically significant ontology classes shared between the first and the third biopsy (p<0.05).

The importance of the genetic factor in the aetiology of premature ovarian failure (POF) is emphasized by the high percentage of familial cases and X chromosome abnormalities account for 10% of chromosomal aberrations. In this study, we report the detailed analysis of 4 chromosomal abnormalities involving the X chromosome and associated with POF th...

Table S3.List of CNVs detected by aCGH of case 4.

Table S2.Microsatellite markers used to identify the breakpoint on chromosome Y.

Table S1.List of BAC and PAC probes used in the study and results of FISH hybridization signal.

Urovysion data. I. Comparison between Urovysion data in two different tumoral areas of the same section II. Comparison between Urovysion data in two different tumoral areas of the same section (DOC)

Clinicopathologic characteristics of 32 tumor samples of the study. Histology/Grade and phase of study are indicated. (DOC)

Gene Ontology. I. Statistically significant (p<0.05) under-representation of gene ontology (GO) categories in HG IN tumors. II. Statistically significant (p<0.05) over-representation of gene ontology (GO) categories in HG IN tumors. III. Statistically significant (p<0.05) under-representation of gene ontology (GO) categories in LG NI tumors. (DOC)

(DOC)

UroVysion test results on freshly isolated interphasic nuclei (FIN) and on formalin fixed paraffin embedded nuclei (FFPE). (DOC)

Copy number alterations (CNA) shared (plus sign) among 10 TCC samples analyzed by array-CGH. NI-TCCs are indicated in italics; IN-TCCs are indicated in bold. For Histology/Grade see Table S1. (DOC)

Bladder carcinogenesis is believed to follow two alternative pathways driven by the loss of chromosome 9 and the gain of chromosome 7, albeit other nonrandom copy number alterations (CNAs) were identified. However, confirmation studies are needed since many aspects of this model remain unclear and considerable heterogeneity among cases has emerged....

Small supernumerary marker chromosomes (sSMCs) are structurally abnormal extra chromosomes that cannot be unambiguously identified or characterized by conventional banding techniques alone, and they are generally equal in size or smaller than chromosome 20 of the same metaphase spread. Small supernumerary ring chromosomes (sSRCs), a smaller class o...