Maria de Fatima Bonaldo

Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, United States

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Publications (79)528.77 Total impact

  • Cancer Research 10/2014; 74(19 Supplement):3111-3111. DOI:10.1158/1538-7445.AM2014-3111 · 9.28 Impact Factor
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    ABSTRACT: Atypical teratoid/rhabdoid tumors (AT/RTs) are aggressive brain tumors that are commonly associated with a dismal prognosis. However, there have been isolated reports of long-term survivors, which were not necessarily correlated with other prognostic factors such as age, clinical stage or extent of surgical resection. Here, we report the case of a 6 year-old boy with AT/RT that remained disease free for 8 years after undergoing subtotal surgical resection followed only by radiation therapy. Upon recurrence, the tumor rapidly progressed leading to patient’s death a short time later. In order to further characterize this case and learn more about the tumor biology of long-term-survivors, we compared the gene expression (GE) profiles from representative samples obtained from primary, recurrent and progressive disease tumors of the above-mentioned patient along with a cohort of primary untreated AT/RT samples, using cDNA microarrays. Global GE analysis and unsupervised hierarchical clustering showed these 3 events clustering together and distinctly apart from the rest of the samples. This indicates a GE background, which is maintained throughout the course of the disease. This unique case suggests that there may be specific clinical characteristics associated with distinctive molecular subtypes of AT/RT. The identification and characterization of AT/RT subtypes could lead to advances in both prognosis and treatment of these tumors.
    Cancer Genetics 09/2014; DOI:10.1016/j.cancergen.2014.05.009 · 2.42 Impact Factor
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    Journal of Neuro-Oncology 02/2014; 118(1). DOI:10.1007/s11060-014-1406-5 · 2.79 Impact Factor
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    ABSTRACT: Malignant rhabdoid tumors (MRT) can occur in a variety of anatomical sites. The most frequent locations are the brain, where they are named atypical teratoid/rhabdoid tumors (AT/RT), and the kidney, where they are named rhabdoid tumors of the kidney (RTK). MRTs at all sites are recognized as the same entity due to their similar morphology, aggressive behavior, and a common genetic abnormality, an inactivating mutation of the SMARCB1/INI-1/hSNF5/BAF47 gene. We aim to investigate potential molecular differences between AT/RT and RTK. We analyzed the microRNA (miRNA) and gene expression (GE) profiles of 10 RTK, 13 AT/RT, and 2 human MRT cell lines (G401-RTK and MON-AT/RT). Illumina V2 MicroRNA Chips (Illumina, Inc., CA, USA) were used for miRNA analysis, and Illumina HT-12 whole genome expression arrays were used for GE analysis. The distribution of p values from GE showed a significant difference between RTK and AT/RT, with 20 % of the genes having p values ≤0.05 and the principal component analysis of the GE data showed separation between RTK and AT/RT. However, the miRNA expression failed to identify the different tumor groups. Among the 122 genes significantly differentially expressed between AT/RT and RTK, we found both genes related to brain development (i.e., FABP7, 22-fold increase in AT/RT) and genes related to kidney development (i.e., TCF21, sixfold increase in RTK). Based on our results, we hypothesized that although MRT are indeed the same tumor, independent of the site of origin, the GE differences reflect the influence of microenvironment over tumor development.
    Child s Nervous System 09/2013; DOI:10.1007/s00381-013-2268-4 · 1.16 Impact Factor
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    ABSTRACT: In vitro neural differentiation of human embryonic stem cells (hESCs) is an advantageous system for studying early neural development. The process of early neural differentiation in hESCs begins by initiation of primitive neuroectoderm, which is manifested by rosette formation, with consecutive differentiation into neural progenitors and early glial-like cells. In this study, we examined the involvement of early neural markers - OTX2, PAX6, Sox1, Nestin, NR2F1, NR2F2, and IRX2 - in the onset of rosette formation, during spontaneous neural differentiation of hESC and human induced pluripotent stem cell (hiPSC) colonies. This is in contrast to the conventional way of studying rosette formation, which involves induction of neuronal differentiation and the utilization of embryoid bodies. Here we show that OTX2 is highly expressed at the onset of rosette formation, when rosettes comprise no more than 3-5 cells, and that its expression precedes that of established markers of early neuronal differentiation. Importantly, the rise of OTX2 expression in these cells coincides with the down-regulation of the pluripotency marker OCT4. Lastly, we show that cells derived from rosettes that emerge during spontaneous differentiation of hESCs or hiPSCs are capable of differentiating into dopaminergic neurons in vitro, and into mature-appearing pyramidal and serotonergic neurons weeks after being injected into the motor cortex of NOD-SCID mice.
    Gene 08/2013; 534(2). DOI:10.1016/j.gene.2013.07.101 · 2.08 Impact Factor
  • Cancer Research 08/2013; 73(8 Supplement):794-794. DOI:10.1158/1538-7445.AM2013-794 · 9.28 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2013; 131(2):AB136. DOI:10.1016/j.jaci.2012.12.1151 · 11.25 Impact Factor
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    ABSTRACT: PURPOSE: Atypical teratoid rhabdoid tumors (ATRTs) are rare, highly malignant central nervous system tumors that occur during infancy and early childhood. Their poor outcome and resistance to conventional chemotherapies and radiotherapy, urges the development of new therapies. Recent studies have evaluated the effects of histone deacetylase inhibitors (HDACi) as a new potential treatment for ATRTs. However, most HDACi act unselectively against all, or at least several, histone deacetylase (HDAC) family members. We hypothesized that specific HDAC family members are deregulated in ATRT and therefore a more selective class of HDACi would be beneficial to patients with ATRT. METHODS: To test our hypothesis, we evaluated the expression level of different HDAC family members in ATRTs. Eight ATRTs were compared to six medulloblastoma samples in regards to the level of expression of the 18 HDAC family members as determined by microarray gene expression profiling. RESULTS: HDAC1 was the only member of the HDAC family to be significantly differentially expressed in ATRTs (FC = 4.728; p value = 0.00003). CONCLUSIONS: A class of HDACi specifically targeting HDAC1 may allow for the desired therapeutic benefits with fewer side effects for children with ATRT.
    Child s Nervous System 11/2012; DOI:10.1007/s00381-012-1965-8 · 1.16 Impact Factor
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    ABSTRACT: Microbial eukaryotes may extinguish much of their nuclear phylogenetic history due to endosymbiotic/horizontal gene transfer (E/HGT). We studied E ⁄ HGT in 32,110 contigs of expressed sequence tags (ESTs) from the dinoflagellate Alexandrium tamarense (Dinophyceae) using a conservative phylogenomic approach. The vast majority of predicted proteins (86.4%) in this alga are novel or dinoflagellate-specific. We searched for putative homologs of these predicted proteins against a taxonomically broadly sampled protein database that includes all currently available data from algae and protists, and reconstructed a phylogeny from each of the putative homologous protein sets. Of the 2,523 resulting phylogenies, 14%-17% are potentially impacted by E/HGT involving both prokaryote and eukaryote lineages, with 2%-4% showing clear evidence of reticulate evolution. The complex evolutionary histories of the remaining proteins, many of which may also have been affected by E/HGT, cannot be interpreted using our approach with currently available gene data. We present empirical evidence of reticulate genome evolution that combined with inadequate or highly complex phylogenetic signal in many proteins may impede genome-wide approaches to infer the tree of microbial eukaryotes.
    Journal of Phycology 10/2012; 48(5):1130-1142. DOI:10.1111/j.1529-8817.2012.01194.x · 2.53 Impact Factor
  • Cancer Research 06/2012; 72(8 Supplement):3002-3002. DOI:10.1158/1538-7445.AM2012-3002 · 9.28 Impact Factor
  • Cancer Research 06/2012; 72(8 Supplement):198-198. DOI:10.1158/1538-7445.AM2012-198 · 9.28 Impact Factor
  • 03/2012; 2012(1):4. DOI:10.5339/qproc.2012.stem.1.4
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    ABSTRACT: Chondrosarcomas are among the most malignant skeletal tumors. Dedifferentiated chondrosarcoma is a highly aggressive subtype of chondrosarcoma, with lung metastases developing within a few months of diagnosis in 90% of patients. In this paper we performed comparative analyses of the transcriptomes of five individual metastatic lung lesions that were surgically resected from a patient with dedifferentiated chondrosarcoma. We document for the first time a high heterogeneity of gene expression profiles among the individual lung metastases. Moreover, we reveal a signature of "multifunctional" genes that are expressed in all metastatic lung lesions. Also, for the first time, we document the occurrence of massive macrophage infiltration in dedifferentiated chondrosarcoma lung metastases.
    Sarcoma 02/2012; 2012:820254. DOI:10.1155/2012/820254
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    ABSTRACT: De novo retrotransposition of Alu elements has been recognized as a major driver for insertion polymorphisms in human populations. In this study, we exploited Alu-anchored bisulfite PCR libraries to identify evolutionarily recent Alu element insertions, and to investigate their genetic and epigenetic variation. A total of 327 putatively recent Alu insertions were identified, altogether represented by 1,762 sequence reads. Nearly all such de novo retrotransposition events (316/327) were novel. Forty-seven out of forty-nine randomly selected events, corresponding to nineteen genomic loci, were sequence-verified. Alu element insertions remained hemizygous in one or more individuals in sixteen of the nineteen genomic loci. The Alu elements were found to be enriched for young Alu families with characteristic sequence features, such as the presence of a longer poly(A) tail. In addition, we documented the occurrence of a duplication of the AT-rich target site in their immediate flanking sequences, a hallmark of retrotransposition. Furthermore, we found the sequence motif (TT/AAAA) that is recognized by the ORF2P protein encoded by LINE-1 in their 5'-flanking regions, consistent with the fact that Alu retrotransposition is facilitated by LINE-1 elements. While most of these Alu elements were heavily methylated, we identified an Alu localized 1.5 kb downstream of TOMM5 that exhibited a completely unmethylated left arm. Interestingly, we observed differential methylation of its immediate 5' and 3' flanking CpG dinucleotides, in concordance with the unmethylated and methylated statuses of its internal 5' and 3' sequences, respectively. Importantly, TOMM5's CpG island and the 3 Alu repeats and 1 MIR element localized upstream of this newly inserted Alu were also found to be unmethylated. Methylation analyses of two additional genomic loci revealed no methylation differences in CpG dinucleotides flanking the Alu insertion sites in the two homologous chromosomes, irrespective of the presence or absence of the insertion. We anticipate that the combination of methodologies utilized in this study, which included repeat-anchored bisulfite PCR sequencing and the computational analysis pipeline herein reported, will prove invaluable for the generation of genetic and epigenetic variation maps.
    BMC Genomics 12/2011; 12:617. DOI:10.1186/1471-2164-12-617 · 4.04 Impact Factor
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    ABSTRACT: We have examined expression of microRNAs (miRNAs) in ependymomas to identify molecular markers of value for clinical management. miRNAs are non-coding RNAs that can block mRNA translation and affect mRNA stability. Changes in the expression of miRNAs have been correlated with many human cancers. We have utilized TaqMan Low Density Arrays to evaluate the expression of 365 miRNAs in ependymomas and normal brain tissue. We first demonstrated the similarity of expression profiles of paired frozen tissue (FT) and paraffin-embedded specimens (FFPE). We compared the miRNA expression profiles of 34 FFPE ependymoma samples with 8 microdissected normal brain tissue specimens enriched for ependymal cells. miRNA expression profiles were then correlated with tumor location, histology and other clinicopathological features. We have identified miRNAs that are over-expressed in ependymomas, such as miR-135a and miR-17-5p, and down-regulated, such as miR-383 and miR-485-5p. We have also uncovered associations between expression of specific miRNAs which portend a worse prognosis. For example, we have identified a cluster of miRNAs on human chromosome 14q32 that is associated with time to relapse. We also found that miR-203 is an independent marker for relapse compared to the parameters that are currently used. Additionally, we have identified three miRNAs (let-7d, miR-596 and miR-367) that strongly correlate to overall survival. We have identified miRNAs that are differentially expressed in ependymomas compared with normal ependymal tissue. We have also uncovered significant associations of miRNAs with clinical behavior. This is the first report of clinically relevant miRNAs in ependymomas.
    PLoS ONE 10/2011; 6(10):e25114. DOI:10.1371/journal.pone.0025114 · 3.53 Impact Factor
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    ABSTRACT: A limited number of reports have investigated the role of microRNAs in osteosarcoma. In this study, we performed miRNA expression profiling of osteosarcoma cell lines, tumor samples, and normal human osteoblasts. Twenty-two differentially expressed microRNAs were identified using high throughput real-time PCR analysis, and 4 (miR-135b, miR-150, miR-542-5p, and miR-652) were confirmed and validated in a different group of tumors. Both miR-135b and miR-150 have been previously shown to be important in cancer. We hypothesize that dysregulation of differentially expressed microRNAs may contribute to tumorigenesis. They might also represent molecular biomarkers or targets for drug development in osteosarcoma.
    Sarcoma 07/2011; 2011:732690. DOI:10.1155/2011/732690
  • Pediatric Blood & Cancer 07/2011; 57(1):183-4. DOI:10.1002/pbc.23105 · 2.56 Impact Factor
  • Cancer Research 07/2011; 71(8 Supplement):3009-3009. DOI:10.1158/1538-7445.AM2011-3009 · 9.28 Impact Factor
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    ABSTRACT: Genomic DNA methylation contributes substantively to transcriptional regulations that underlie mammalian development and cellular differentiation. Much effort has been made to decipher the molecular mechanisms governing the establishment and maintenance of DNA methylation patterns. However, little is known about genome-wide variation of DNA methylation patterns. In this study, we introduced the concept of methylation entropy, a measure of the randomness of DNA methylation patterns in a cell population, and exploited it to assess the variability in DNA methylation patterns of Alu repeats and promoters. A few interesting observations were made: (i) within a cell population, methylation entropy varies among genomic loci; (ii) among cell populations, the methylation entropies of most genomic loci remain constant; (iii) compared to normal tissue controls, some tumors exhibit greater methylation entropies; (iv) Alu elements with high methylation entropy are associated with high GC content but depletion of CpG dinucleotides and (v) Alu elements in the intronic regions or far from CpG islands are associated with low methylation entropy. We further identified 12 putative allelic-specific methylated genomic loci, including four Alu elements and eight promoters. Lastly, using subcloned normal fibroblast cells, we demonstrated the highly variable methylation patterns are resulted from low fidelity of DNA methylation inheritance.
    Nucleic Acids Research 05/2011; 39(10):4099-108. DOI:10.1093/nar/gkr017 · 9.11 Impact Factor
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    ABSTRACT: The identification of molecular signatures predictive of clinical behavior and outcome in brain tumors has been the focus of many studies in the recent years. Despite the wealth of data that are available in the public domain on alterations in the genome, epigenome and transcriptome of brain tumors, the underlying molecular mechanisms leading to tumor initiation and progression remain largely unknown. Unfortunately, most of these data are scattered in multiple databases and supplementary materials of publications, thus making their retrieval, evaluation, comparison and visualization a rather arduous task. Here we report the development and implementation of an open access database (BTECH), a community resource for the deposition of a wide range of molecular data derived from brain tumor studies. This comprehensive database integrates multiple datasets, including transcript profiles, epigenomic CpG methylation data, DNA copy number alterations and structural chromosomal rearrangements, tumor-associated gene lists, SNPs, genomic features concerning Alu repeats and general genomic annotations. A genome browser has also been developed that allows for the simultaneous visualization of the different datasets and the various annotated features. Besides enabling an integrative view of diverse datasets through the genome browser, we also provide links to the original references for users to have a more accurate understanding of each specific dataset. This integrated platform will facilitate uncovering interactions among genetic and epigenetic factors associated with brain tumor development. BTECH is freely available at Electronic supplementary material The online version of this article (doi:10.1007/s12021-010-9091-9) contains supplementary material, which is available to authorized users.
    Neuroinformatics 03/2011; 9(1):59-67. DOI:10.1007/s12021-010-9091-9 · 3.10 Impact Factor

Publication Stats

6k Citations
528.77 Total Impact Points


  • 2013–2014
    • Ann & Robert H. Lurie Children's Hospital of Chicago
      Chicago, Illinois, United States
  • 2006–2013
    • Northwestern University
      • • Feinberg School of Medicine
      • • Cancer Biology and Epigenomics Program
      • • Department of Pediatrics
      Evanston, Illinois, United States
    • University of Chicago
      Chicago, Illinois, United States
  • 2009–2011
    • Children's Memorial Medical Center
      Chicago, Illinois, United States
    • Children's Memorial Hospital
      Chicago, Illinois, United States
  • 1999–2010
    • University of Iowa
      • Department of Pediatrics
      Iowa City, Iowa, United States
  • 1996–1998
    • Columbia University
      • • Department of Psychiatry
      • • JP Sulzberger Columbia Genome Center
      New York City, New York, United States
  • 1997
    • New York State Psychiatric Institute
      New York City, New York, United States