Biomedical subjects

Maria Zielenska

Publications and source records attributed to Maria Zielenska.

30 records · Page 2Linked to original sources

PubMed2005

Association of drowning and myocarditis in a pediatric population: an autopsy-based study.

CONTEXT: Drowning is a frequent cause of accidental death in childhood, but the association of myocarditis and drowning has only rarely been reported. OBJECTIVE: To report 5 cases of drowning in children with coexistent myocarditis. DESIGN: A retrospective review of autopsy records of patients 0 years to 18 years of age was performed during a 6-year period (1998-2003, total cases reviewed = 1431). RESULTS: Twenty-two drownings were identified, in 14 male and 8 female children. Five patients (23%), 3 female and 2 male children, had coexistent myocarditis. The 5 patients ranged in age from 23 months to 13 years (mean, 7 years 2 months). None of the patients had antecedent symptomatology suggestive of myocarditis. In all patients, the myocarditis was focal mild or moderate, and the inflammatory infiltrate comprised lymphocytes with smaller numbers of neutrophils. All 5 patients had foci of myocyte necrosis. One patient had histologic evidence of myocardial hypertrophy but no evidence of a cardiomyopathy. Microbiologic studies, including culture, immunohistochemistry, polymerase chain reaction, and reverse transcriptase polymerase chain reaction, revealed Mycoplasma pneumoniae DNA in 1 case. CONCLUSIONS: The finding of myocarditis in a significant proportion of drowning victims in this series highlights the importance of a thorough autopsy examination in apparently straightforward cases and has clinicopathologic significance.

Adolescent↗

PubMed2004

Primary subcutaneous primitive neuroectodermal tumor with aggressive behavior and an unusual karyotype: case report.

Primitive neuroectodermal tumor/Ewing sarcoma (PNET/ES) rarely occurs in the skin and subcutaneous tissues. We present a case of a 16-year-old girl with primary cutaneous and subcutaneous PNET/ES of the abdominal wall. Despite wide local excision and chemotherapy, she rapidly developed cranial bone and brain metastases, followed by lung and skeletal metastases, and died shortly thereafter. The recurrent tumor exhibited light microscopic features of a small, round, blue cell tumor with intracytoplasmic glycogen. Immunohistochemical analysis showed positivity for CD99, CD56, S100, and glial fibrillary acid protein, and ultrastructural features included cytoplasmic glycogen and focal complex interdigitating synaptic junction-like cytoplasmic folds. Cytogenetic analysis of the relapsed tumor showed a complex karyotype: 47,XX,i(1)(q10), der(4)t(4;19) (q33 approximately q35;q13.1), + 8,t(15;17)(q24;p11.2 approximately p12),der(19)t (19;20)(q13.1;p11.2),der(22)t(20;22)(q13;q13). Cytogenetic, interphase fluorescence in situ hybridization, and molecular genetic analyses failed to show t(11:22) (q24;q12) or abnormalities of chromosome region 22q12. The clinical behavior and atypical and complex cytogenetic abnormalities exhibited by the tumor in this patient are unusual and represent the most aggressive end of the clinical spectrum of cutaneous and subcutaneous PNET/ES.

Adolescent↗

PubMed2004

C-kit expression and mutational analysis in medulloblastoma.

The proto-oncogene c-kit is a receptor tyrosine kinase recognized to initiate essential signal transduction pathways that transmit biological signals for cellular proliferation, differentiation, and metastasis. Aberrant expression or mutation of c-kit has been shown to be involved in the pathogenesis of many cancers. Studies using imatinib mesylate (STI 571, Gleevec, Novartis, East Hannover, NJ, USA), an inhibitor of the tyrosine kinases brc-abl, c-kit, and PDGFR, have shown significant response in patients with chronic myelogenous leukemia and gastrointestinal stromal tumor. With the aim of identifying additional groups of tumors that may use the stem cell factor/c-kit pathway and, secondarily, may be responsive to imatinib mesylate treatment, we looked at the expression of c-kit in medulloblastoma. Medulloblastoma, a highly invasive primitive neuroectodermal tumor of the cerebellum, is the most common, malignant central nervous system tumor of childhood. Histologic features of medulloblastoma have failed to provide an accurate prediction of the clinical-biological behavior of these tumors. Characterizing the genetic events that play a role in the biology of these tumors may allow for molecular sub-typing and could lead to the development of novel therapeutic strategies. This study evaluated c-kit expression and mutational status in 10 medulloblastoma tumor samples. All 10 medulloblastoma tumors expressed c-kit by reverse transcriptase-polymerase chain reaction and 9 by immunohistochemical analysis. All tumor samples were screened for mutations in exons 9, 11, and 13 of the c-kit gene by direct sequencing. No sequence abnormalities were detected in these exons. These experiments lead us to the conclusion that c-kit activation in medulloblastoma is independent of mutation.

Adolescent↗

PubMed2004

Combined spectral karyotyping, multicolor banding, and microarray comparative genomic hybridization analysis provides a detailed characterization of complex structural chromosomal rearrangements associated with gene amplification in the osteosarcoma cell line MG-63.

The advancement of fluorescence in situ hybridization-based assays has permitted more refined delineation of chromosomal loci involved in complex chromosomal rearrangements (CCRs) and gene amplification. In this detailed molecular cytogenetic analysis, spectral karyotyping (SKY), multicolor banding (mBAND) analysis, and microarray comparative genomic hybridization (CGH) were used to refine the analysis of chromosomes with amplifications and small intrachromosomal rearrangements such as inverted duplications and interstitial deletions present in the osteosarcoma cell line MG-63. SKY analysis has limited resolving power to delineate cryptic chromosomal rearrangements, so mBAND assays were performed for a subset of chromosomes (i.e., 6, 8, 17, and 20). Of the 10 clonal CCRs analyzed in detail with mBAND, 5 were found to have rearrangements between 8q24 and either 6p23 approximately pter or 6p21, with multiple copies of this translocation inserted at various sites in the different chromosomes. In two CCRs, 6p21 and 8q24 generated an alternating pattern of mBAND probe hybridization, indicating the presence of a large coamplified repeat unit within homogeneously staining regions. Microarray CGH analysis demonstrated focal high-level amplification of 8q23 approximately q24, 6p22 approximately pter, and 6p21, in agreement with the pattern of chromosome subband gains identified with mBAND. Thus, sequential SKY, mBAND, and microarray CGH provided a comprehensive description of some of the intricate chromosomal aberrations present in the complex MG-63 karyotype and permitted reconstruction of the fine structure of the genomic rearrangements, thus providing some important mechanistic clues concerning the details of the amplification process in tumors.

Bone Neoplasms↗

PubMed2004

Defining a 0.5-mb region of genomic gain on chromosome 6p22 in bladder cancer by quantitative-multiplex polymerase chain reaction.

Metaphase-based comparative genomic hybridization (CGH) has identified recurrent regions of gain on different chromosomes in bladder cancer, including 6p22. These regions may contain activated oncogenes important in disease progression. Using quantitative multiplex polymerase chain reaction (QM-PCR) to study DNA from 59 bladder tumors, we precisely mapped the focal region of genomic gain on 6p22. The marker STS-X64229 had copy number increases in 38 of 59 (64%) tumors and the flanking markers, RH122450 and A009N14, had copy number gains in 33 of 59 (56%) and 26 of 59 (45%) respectively. Contiguous gain was present for all three markers in 14 of 59 (24%) and for two (RH122450 and STS-X64229) in 25 of 59 (42%). The genomic distance between the markers flanking STS-X64229 is 0.5 megabases, defining the minimal region of gain on 6p22. Locus-specific interphase fluorescence in situ hybridization confirmed the increased copy numbers detected by QM-PCR. Current human genomic mapping data indicates that an oncogene, DEK, is centrally placed within this minimal region. Our findings demonstrate the power of QM-PCR to narrow the regions identified by CGH to facilitate identifying specific candidate oncogenes. This also represents the first study identifying DNA copy number increases for DEK in bladder cancer.

Adult↗

PubMed2004

Comparative genomic hybridization analysis of pediatric adamantinomatous craniopharyngiomas and a review of the literature.

OBJECT: The purpose of this study was to examine chromosomal gains and losses in 11 pediatric adamantinomatous craniopharyngiomas by using comparative genomic hybridization (CGH), as well as to review the cytogenetic literature that has contributed to the characterization of these tumors. One source of confusion in the cytogenetic and CGH literature concerning craniopharyngioma is that the authors of most studies fail to distinguish between pediatric and later-onset forms of the disease. Thus, this study was focused on pediatric craniopharyngioma. METHODS: To determine an overview of the genetic events leading to the development of these tumors, 10 adamantinomatous craniopharyngiomas were analyzed using CGH; none of the tumor specimens demonstrated gains or losses of DNA sequence. CONCLUSIONS: In view of these findings as well as those published in the majority of previous cytogenetic studies of craniopharyngiomas, the authors conclude that the recurrent acquisition of chromosomal imbalances does not play a major role in tumorigenesis and that chromosomal gains and losses are a relatively rare event in primary tumors of pediatric origin.

Adolescent↗

PubMed2003

Spectral karyotyping identifies recurrent complex rearrangements of chromosomes 8, 17, and 20 in osteosarcomas.

Conventional cytogenetic studies have shown that osteosarcomas (OSs) are often highly aneuploid, with a large number of both structural and numerical chromosomal alterations. To investigate the complexity of OS karyotypes in detail, we applied spectral karyotyping (SKY) to a series of 14 primary OS tumors and four established OS cell lines. A total of 531 rearrangements were identified by SKY, of which 300 breakpoints could be assigned to a specific chromosome band. There was an average of 38.5 breakpoints identified by SKY per primary tumor. Chromosome 20 was involved in a disproportionately high number of structural rearrangements, with 38 different aberrations being detected. Chromosomal rearrangements between chromosomes 20 and 8 were evident in four tumors. FISH analysis using a 20q13 subtelomeric probe identified frequent involvement of 20q in complex structural rearrangements of OS cell lines. Characterization of the structural aberrations of chromosomes 8 and 17 by use of SKY demonstrated frequent duplication or partial gains of chromosome bands 8q23-24 and 17p11-13. Other chromosomes frequently involved in structural alteration were chromosomes 1 (47 rearrangements) and 6 (38 rearrangements). Centromeric rearrangements often involving chromosomes 1, 6, 13, 14, 17, and 20 were present. Four of the 14 primary OS tumors were characterized by nonclonal changes that included both structural and numerical alterations. In summary, OS tumors have a very high frequency of structural and numerical alterations, compounded by gross changes in ploidy. This intrinsic karyotype instability leads to a diversity of rearrangements and the acquisition of composite chromosomal rearrangements, with the highest frequency of alteration leading to gain of 8q23-24 and 17p11-13 and rearrangement of 20q. These findings suggest that specific sequences mapping to these chromosomal regions will likely have a role in the development and progression of OS.

Adolescent↗

PubMed2003

High-resolution mapping of amplifications and deletions in pediatric osteosarcoma by use of CGH analysis of cDNA microarrays.

Conventional cytogenetic and comparative genomic hybridization (CGH) studies have shown that osteosarcomas (OSs) are characterized by complex structural and numerical chromosomal alterations and gene amplification. In this study, we used high-resolution CGH to investigate recurrent patterns of genomic imbalance by use of DNA derived from nine OS tumors hybridized to a 19,200-clone cDNA microarray. In six OSs, there was copy number gain or amplification of 6p, with a minimal region of gain centering on segment 6p12.1. In seven OSs, the pattern of amplification affecting chromosome arm 8q showed high-level gains of 8q12-21.3 and 8q22-q23, with amplification of the MYC oncogene at 8q24.2. Seven OSs showed copy number gain or amplification of 17p between the loci bounded by GAS7 and PMI (17p11.2-17p12), and three of these tumors also showed small losses at 17p13, including the region containing TP53. An in silico analysis of the distribution of segmental duplications (duplicons) in this region identified a large number of tracts consisting of paralogous sequences mapping to the 17p region, encompassing the region of deletions and amplifications in OS. Interestingly, within this same region there were clusters of duplicons and several genes that are expressed during bone morphogenesis and in OS. In summary, microarray CGH analysis of the chromosomal imbalances of OS confirm the overall pattern observed by use of metaphase CGH and provides a more precise refinement of the boundaries of genomic gains and losses that characterize this tumor.

Adolescent↗

PubMed2003

Retroperitoneal infantile fibrosarcoma: clinical, molecular, and therapeutic aspects of an unusual tumor.

The authors describe a patient with a large retroperitoneal infantile fibrosarcoma that responded well to preoperative chemotherapy, which subsequently facilitated the complete surgical resection of the mass. The patient had an unusual site of metastasis presumed to be to a regional lymph node. The histology on initial core biopsies was not classic but showed a round cell, myxoid pattern. The presence of the t(12;15)(p13;q25) and the fusion transcript ETV6-NTRK3 by RTPCR facilitated the diagnosis.

Female↗

PubMed2002

Identification of a novel gene NCRMS on chromosome 12q21 with differential expression between rhabdomyosarcoma subtypes.

Rhabdomyosarcoma (RMS) is a malignant soft tissue tumor showing varying degrees of skeletal muscle differentiation. Two major histologic subtypes exist, alveolar and embryonal, each with associated molecular genetic changes. We have used Representational Difference Analysis (RDA) to compare gene expression between the two RMS subtypes and have identified the novel gene NCRMS (non-coding RNA in RMS) that has increased expression in the alveolar subtype relative to the embryonal subtype. Multiple alternatively spliced forms of NCRMS were identified through library screening, RACE, and comparison to human expressed sequence tags (ESTs). Northern blot analysis indicated the transcript size to be 1.25 kb in alveolar RMS. There was no sequence homology to any of the known genes in GenBank, but extensive homology to ESTs from various species. Comparison to human genomic sequences identified at least 11 exons mapping to chromosomal region 12q21. Differential expression of NCRMS was noted between various tumor types. Since NCRMS RNA possesses limited potential for protein coding, yet with conserved sequences between different species, it is likely that NCRMS is a functional non-coding RNA. Known genes in its proximity include myogenic regulators Myf5 and Myf6, growth factor Igf1, and another potential differentially expressed gene (ATP2B1) in RMS isolated by RDA.

Alanine Racemase↗

PubMed2002

Identification of numerical chromosomal changes detected by interphase fluorescence in situ hybridization in high-grade prostate intraepithelial neoplasia as a predictor of carcinoma.

CONTEXT: High-grade prostate intraepithelial neoplasia (HPIN) is the most likely precursor of prostate cancer. The condition of many patients with a diagnosis of HPIN in prostate needle core biopsy could, if left untreated, progress to invasive cancer. Currently there is no available clinical, immunohistochemical, or morphologic criteria that are predictive of this progression. OBJECTIVE: To determine whether chromosomal instability in these precursor lesions could increase their predictive value for cancer detection. DESIGN: Dual-color interphase fluorescence in situ hybridization analysis was performed on archived prostate needle core biopsies from 54 patients with initial diagnosis of isolated HPIN and follow-up of 3 years or more. We used commercially available centromere probes for chromosomes 4, 7, 8, and 10. We had interpretable results in 44 patients as follows: (1) group A: 24 HPIN patients with persistent HPIN and/or benign lesions in the follow-up biopsies, and (2) group B: 20 HPIN patients with progression to prostate carcinoma. RESULTS: Twenty-five percent of the patients in group B displayed numeric chromosomal aberrations. Only 8.3% of the patients from group A had chromosomal abnormalities (P =.1). The observed overall chromosomal changes in HPIN were higher than those in normal or hyperplastic epithelium, with a statistically significant difference (P <.05). All aberrations were detected in the form of chromosomal gain. Overall, the commonest aberration was gain of chromosome 8, followed by gains of chromosomes 7 and 10. CONCLUSION: These results indicated that although no single numeric chromosomal abnormality could be assigned as a predictor of HPIN progression to carcinoma, the overall level of numeric chromosomal abnormalities shows a trend of elevation in HPIN patients whose condition subsequently progressed to carcinoma.

Aged↗

PubMedDate not supplied

Chromosomal localization of DNA amplifications in neuroblastoma tumors using cDNA microarray comparative genomic hybridization.

Conventional comparative genomic hybridization (CGH) profiling of neuroblastomas has identified many genomic aberrations, although the limited resolution has precluded a precise localization of sequences of interest within amplicons. To map high copy number genomic gains in clinically matched stage IV neuroblastomas, CGH analysis using a 19,200-feature cDNA microarray was used. A dedicated (freely available) algorithm was developed for rapid in silico determination of chromosomal localizations of microarray cDNA targets, and for generation of an ideogram-type profile of copy number changes. Using these methodologies, novel gene amplifications undetectable by chromosome CGH were identified, and larger MYCN amplicon sizes (in one tumor up to 6 Mb) than those previously reported in neuroblastoma were identified. The genes HPCAL1, LPIN1/KIAA0188, NAG, and NSE1/LOC151354 were found to be coamplified with MYCN. To determine whether stage IV primary tumors could be further subclassified based on their genomic copy number profiles, hierarchical clustering was performed. Cluster analysis of microarray CGH data identified three groups: 1) no amplifications evident, 2) a small MYCN amplicon as the only detectable imbalance, and 3) a large MYCN amplicon with additional gene amplifications. Application of CGH to cDNA microarray targets will help to determine both the variation of amplicon size and help better define amplification-dependent and independent pathways of progression in neuroblastoma.

Algorithms↗