Bekim Sadikovic

Western University, London, Ontario, Canada

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Publications (35)124.92 Total impact

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    ABSTRACT: Genomic, chromosomal, and gene-specific changes in the DNA sequence underpin both phenotypic variations in populations as well as disease associations, and the application of genomic technologies for the identification of constitutional (inherited) or somatic (acquired) alterations in DNA sequence forms a cornerstone of clinical and molecular genetics. In addition to the disruption of primary DNA sequence, the modulation of DNA function by epigenetic phenomena, in particular by DNA methylation, has long been known to play a role in the regulation of gene expression and consequent pathogenesis. However, these epigenetic factors have been identified only in a handful of pediatric conditions, including imprinting disorders. Technological advances in the past decade that have revolutionized clinical genomics are now rapidly being applied to the emerging discipline of clinical epigenomics. Here, we present an overview of epigenetic mechanisms with a focus on DNA modifications, including the molecular mechanisms of DNA methylation and subtypes of DNA modifications, and we describe the classic and emerging genomic technologies that are being applied to this study. This review focuses primarily on constitutional epigenomic conditions associated with a spectrum of developmental and intellectual disabilities. Epigenomic disorders are discussed in the context of global genomic disorders, imprinting disorders, and single gene disorders. We include a section focused on integration of genetic and epigenetic mechanisms together with their effect on clinical phenotypes. Finally, we summarize emerging epigenomic technologies and their impact on diagnostic aspects of constitutional genetic and epigenetic disorders.
    No preview · Article · Jan 2016 · Critical Reviews in Clinical Laboratory Sciences
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    ABSTRACT: achieving a major molecular response (MMR) is the goal of imatinib therapy for chronic myeloid leukemia. However, the association between gender, BCR-ABL transcript type, and age with MMR is not well understood and often controversial. we retrospectively analyzed 166 patients who have been treated with imatinib for up to 10 years. males had a lower MMR rate than females (63.3% vs. 81.6%, p = 0.006) and a shorter time to relapse (median 354 vs 675 days, p = 0.049), while patients with b3a2 or with both b3a2 and b2a2 breakpoint transcripts had higher MMR rate than those with b2a2 (81.8%, 77.1% vs. 60.7%, p = 0.023 for b3a2 vs. b2a2, p = 0.043 for both vs. b2a2). A striking difference was found between males with b2a2 and females with both b2a2 and b3a2 in terms of MMR rate (43.8% vs. 88.9%), MMR rate within 6 months (7.1% vs. 62.5%) and the time to MMR (median days 493 vs. 159, p=0.036). both gender and BCR-ABL transcript, but not age, were significantly associated with the molecular response. Males with b2a2 represent a less favorable group in their response to imatinib treatment and may need alternative therapy regimen and closer monitoring. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · Jun 2015 · European Journal Of Haematology
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    ABSTRACT: The aim of this Position Statement is to provide recommendations for Canadian medical geneticists, clinical laboratory geneticists, genetic counsellors and other physicians regarding the use of genome-wide sequencing of germline DNA in the context of clinical genetic diagnosis. This statement has been developed to facilitate the clinical translation and development of best practices for clinical genome-wide sequencing for genetic diagnosis of monogenic diseases in Canada; it does not address the clinical application of this technology in other fields such as molecular investigation of cancer or for population screening of healthy individuals. Two multidisciplinary groups consisting of medical geneticists, clinical laboratory geneticists, genetic counsellors, ethicists, lawyers and genetic researchers were assembled to review existing literature and guidelines on genome-wide sequencing for clinical genetic diagnosis in the context of monogenic diseases, and to make recommendations relevant to the Canadian context. The statement was circulated for comment to the Canadian College of Medical Geneticists (CCMG) membership-at-large and, following incorporation of feedback, approved by the CCMG Board of Directors. The CCMG is a Canadian organisation responsible for certifying medical geneticists and clinical laboratory geneticists, and for establishing professional and ethical standards for clinical genetics services in Canada. Recommendations include (1) clinical genome-wide sequencing is an appropriate approach in the diagnostic assessment of a patient for whom there is suspicion of a significant monogenic disease that is associated with a high degree of genetic heterogeneity, or where specific genetic tests have failed to provide a diagnosis; (2) until the benefits of reporting incidental findings are established, we do not endorse the intentional clinical analysis of disease-associated genes other than those linked to the primary indication; and (3) clinicians should provide genetic counselling and obtain informed consent prior to undertaking clinical genome-wide sequencing. Counselling should include discussion of the limitations of testing, likelihood and implications of diagnosis and incidental findings, and the potential need for further analysis to facilitate clinical interpretation, including studies performed in a research setting. These recommendations will be routinely re-evaluated as knowledge of diagnostic and clinical utility of clinical genome-wide sequencing improves. While the document was developed to direct practice in Canada, the applicability of the statement is broader and will be of interest to clinicians and health jurisdictions internationally. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Full-text · Article · May 2015 · Journal of Medical Genetics
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    ABSTRACT: Hereditary hemochromatosis leads to an increased lifetime risk for end-organ damage due to excess iron deposition. Guidelines recommend that genetic testing be performed in patients with clinical suspicion of iron overload accompanied by elevated serum ferritin and transferrin saturation levels. To evaluate guideline adherence and the clinical and economic impact of HFE genetic testing. The electronic charts of patients submitted for HFE testing in 2012 were reviewed for genetic testing results, biochemical markers of iron overload and clinical history of phlebotomy. A total of 664 samples were sent for testing, with clinical, biochemical and phlebotomy data available for 160 patients. A positive C282Y homozygote or C282Y⁄H63D compound heterozygote test result was observed in 18% of patients. Patients with an at-risk HFE genotype had significantly higher iron saturation, serum iron and hemoglobin (P<0.001), without higher ferritin or liver enzyme levels. Fifty percent of patients referred for testing did not have biochemical evidence of iron overload (transferrin saturation >45% and ferritin level >300 μg⁄L). Patients were four times more likely to undergo phlebotomy if they were gene test positive (RR 4.29 [95% CI 2.35 to 7.83]; P<0.00001). One-half of patients referred for testing did not exhibit biochemical evidence of iron overload. Many patients with biochemical evidence of iron overload, but with negative genetic test results, did not undergo phlebotomy. A requisition to determine clinical indication for testing may reduce the use of the HFE genetic test. Finally, improvement of current genetic test characteristics would improve rationale for the test. A significant proportion of hemochromatosis genetic testing does not adhere to current guidelines and would not alter patient management.
    No preview · Article · Feb 2015 · Canadian journal of gastroenterology = Journal canadien de gastroenterologie
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    ABSTRACT: Malsegregation of chromosomes during reproduction can result in uniparental disomy when associated with trisomy rescue, monosomy rescue or gamete complementation. Pathogenicity stemming from uniparental disomy in liveborns results from imprinting disorders or autozygosity for autosomal recessive disorders. We report on a girl with Prader–Willi syndrome and Tay–Sachs disease resulting from maternal uniparental disomy of chromosome 15. The child also had an isochromosome Xq. To further characterize the etiology of the aberrant chromosome 15 and the isochromosome Xq, SNP loci from both chromosomes were assessed in the proband and parents, and genome-wide DNA methylation analysis was performed. SNP and DNA methylation analysis confirmed maternal uniparental heterodisomy around the Prader–Willi locus, while the region around the HEXA locus showed maternal uniparental isodisomy. This result is consistent with trisomy rescue of a maternal meiosis l error in a chromosome 15 with two meiotic recombinations. SNP analysis of the X chromosomes is consistent with a maternal origin for the isochromosome. © 2014 Wiley Periodicals, Inc.
    No preview · Article · Jan 2015 · American Journal of Medical Genetics Part A
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    ABSTRACT: Angelman syndrome is a neurodevelopmental disorder caused by a deficiency of the imprinted and maternally expressed UBE3A gene. Although de novo genetic and epigenetic imprinting defects of UBE3A genomic locus account for majority of Angelman diagnoses, approximately 10% of individuals affected with Angelman syndrome are a result of UBE3A loss-of-function mutations occurring on the expressed maternal chromosome. The variants described in this manuscript represent the analysis of 2515 patients referred for UBE3A gene sequencing at our institution, along with a comprehensive review of the UBE3A mutation literature. Of these, 267 (10.62%) patients had a report issued for detection of a UBE3A gene nucleotide variant, which in many cases involved family studies resulting in reclassification of variants of unknown clinical significance (VUS). Overall, 111 (4.41%) probands had a nucleotide change classified as pathogenic or strongly favored to be pathogenic, 29 (1.15%) had a variant of unknown clinical significance, and 126 (5.0%) had a nucleotide change classified as benign or strongly favored to be benign. All variants and their clinical interpretations are submitted to NCBI ClinVar, a freely accessible human variation and phenotype database.This article is protected by copyright. All rights reserved
    No preview · Article · Dec 2014 · Human Mutation
  • Matthew B Lanktree · Bekim Sadikovic · Mark A Crowther

    No preview · Article · Oct 2014 · Canadian Medical Association Journal
  • Bekim Sadikovic

    No preview · Article · Jun 2014 · Clinical Biochemistry
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    ABSTRACT: A significant proportion (up to 62%) of Oral Squamous Cell Carcinomas (OSCCs) may arise from oral potential malignant lesions (OPML), such as leukoplakia. Patient outcomes may thus be improved through detection of lesions at risk for malignant transformation, by identifying and categorizing genetic changes in sequential, progressive OPMLs. We conducted array comparative genomic hybridization (aCGH) analysis of 25 sequential, progressive OPMLs and same-site OSCCs from five patients. Recurrent DNA copy number gains were identified on 1p in 20/25 cases (80%) with minimal, high-level amplification regions on 1p35 and 1p36. Other regions of gains were frequently observed: 11q13.4 (68%), 9q34.13 (64%), 21q22.3 (60%), 6p21 and 6q25 (56%), 10q24, 19q13.2, 22q12, 5q31.2, 7p13, 10q24, and 14q22 (48%). DNA losses were observed in >20% of samples and mainly detected on 5q31.2 (35%), 16p13.2 (30%), 9q33.1 and 9q33.29 (25%), and 17q11.2, 3p26.2, 18q21.1, 4q34.1 and 8p23.2 (20%). Such Copy Number Alterations (CNAs) were mapped in all grades of dysplasia that progressed, and their corresponding OSCCs, in 70% of patients, indicating that these CNAs may be associated with disease progression. Amplified genes mapping within recurrent CNAs (KHDRBS1, PARP1, RAB1A, HBEGF, PAIP2, BTBD7) were selected for validation, by quantitative real-time PCR, in an independent set of 32 progressive leukoplakia, 32 OSSCs and 21 non-progressive leukoplakia samples. Amplification of BTBD7, KHDRBS1, PARP1 and RAB1A was exclusively detected in progressive leukoplakia and corresponding OSCC. BTBD7, KHDRBS1, PARP1 and RAB1A may be associated with OSCC progression. Protein-protein interaction networks were created to identify possible pathways associated with OSCC progression.
    Full-text · Article · Jan 2014 · Human Molecular Genetics
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    ABSTRACT: Maternal-effect mutations in NLRP7 cause rare biparentally inherited hydatidiform moles (BiHMs), abnormal pregnancies containing hypertrophic vesicular trophoblast but no embryo. BiHM trophoblasts display abnormal DNA methylation patterns affecting maternally methylated germline differentially methylated regions (gDMRs), suggesting that NLRP7 plays an important role in reprogramming imprinted gDMRs. How NLRP7—a component of the CATERPILLAR family of proteins involved in innate immunity and apoptosis—causes these specific DNA methylation and trophoblast defects is unknown. Because rodents lack NLRP7, we used human embryonic stem cells to study its function and demonstrate that NLRP7 interacts with YY1, an important chromatin-binding factor. Reduced NLRP7 levels alter DNA methylation and accelerate trophoblast lineage differentiation. NLRP7 thus appears to function in chromatin reprogramming and DNA methylation in the germline or early embryonic development, functions not previously associated with members of the NLRP family.
    Preview · Article · Oct 2013 · Human Molecular Genetics
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    ABSTRACT: Osteosarcoma, the most frequent primary bone tumor, is a malignant mesenchymal sarcoma with a peak incidence in young children and adolescents. Left untreated, it progresses relentlessly to local and systemic disease, ultimately leading to death within months. Genomically, osteosarcomas are aneuploid with chaotic karyotypes, lacking the pathognomonic genetic rearrangements characteristic of most sarcomas. The familial genetics of osteosarcoma helped in elucidating some of the etiological molecular disruptions, such as the tumor suppressor genes RB1 in retinoblastoma and TP53 in Li-Fraumeni, and RECQL4 involved in DNA repair/replication in Rothmund-Thomson syndrome. Genomic profiling approaches such as array comparative genomic hybridization (aCGH) have provided additional insights concerning the mechanisms responsible for generating complex osteosarcoma genomes. This chapter provides a brief introduction to the clinical features of conventional osteosarcoma, the predominant subtypes, and a general overview of materials and analytical methods of osteosarcoma aCGH, followed by a more detailed literature overview of aCGH studies and a discussion of emerging genes, molecular mechanisms, and their clinical implications, as well as more recent application of integrative genomics in osteosarcoma. aCHG is helping elucidate genomic events leading to tumor development and evolution as well as identification of prognostic markers and therapeutic targets in osteosarcoma.
    No preview · Article · Feb 2013 · Methods in molecular biology (Clifton, N.J.)
  • Bekim Sadikovic · David I. Rodenhiser
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    ABSTRACT: This chapter contains sections titled: IntroductionEpigenetic modifications: DNA methylationDNA methylation and cancerEpigenetic histone modificationsBenzo(a)pyrene – a prototype PAH and environmental carcinogenMolecular mechanisms of benzopyrene carcinogenicity: geno- and epigeno-toxicityEpigenetic effects of multiple/synergistic carcinogen exposuresSummary and future considerationsAcknowledgmentsReferences
    No preview · Chapter · Aug 2012
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    ABSTRACT: We recently reported a deletion of exon 2 of the trimethyllysine hydroxylase epsilon (TMLHE) gene in a proband with autism. TMLHE maps to the X chromosome and encodes the first enzyme in carnitine biosynthesis, 6-N-trimethyllysine dioxygenase. Deletion of exon 2 of TMLHE causes enzyme deficiency, resulting in increased substrate concentration (6-N-trimethyllysine) and decreased product levels (3-hydroxy-6-N-trimethyllysine and γ-butyrobetaine) in plasma and urine. TMLHE deficiency is common in control males (24 in 8,787 or 1 in 366) and was not significantly increased in frequency in probands from simplex autism families (9 in 2,904 or 1 in 323). However, it was 2.82-fold more frequent in probands from male-male multiplex autism families compared with controls (7 in 909 or 1 in 130; P = 0.023). Additionally, six of seven autistic male siblings of probands in male-male multiplex families had the deletion, suggesting that TMLHE deficiency is a risk factor for autism (metaanalysis Z-score = 2.90 and P = 0.0037), although with low penetrance (2-4%). These data suggest that dysregulation of carnitine metabolism may be important in nondysmorphic autism; that abnormalities of carnitine intake, loss, transport, or synthesis may be important in a larger fraction of nondysmorphic autism cases; and that the carnitine pathway may provide a novel target for therapy or prevention of autism.
    Full-text · Article · May 2012 · Proceedings of the National Academy of Sciences
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    ABSTRACT: Epigenetic mechanisms may play an important role in the developmental programming of adult-onset chronic metabolic diseases resulting from suboptimal fetal nutrition, but the exact molecular mechanisms are incompletely understood. Given the central role of the liver in metabolic regulation, we investigated whether chronic maternal dietary protein restriction has long-term effects on liver gene expression in the offspring. We fed adult C57BL/6J dams ad libitum an 8% maternal low-protein (MLP) or 20% protein control diet (C) from 4 wk prior to mating until the end of lactation. Male pups were weaned to standard nonpurified diet and singly housed at 21 d of age (d 21). Body weights were followed to 1 y of age (1 y). At d 21 and 1 y, organs were quantitatively dissected and analyzed. MLP offspring had significantly lower body weights at all ages and significantly lower serum activity of alanine aminotransferase and lactate dehydrogenase at 1 y. Gene expression profiling of liver at 1 y showed 521 overexpressed and 236 underexpressed genes in MLP compared to C offspring. The most important novel finding was the overexpression of genes found in liver that participate in organization and maintenance of higher order chromatin architecture and regulation of transcriptional activation. These included members of the cohesin-mediator complex, which regulate gene expression by forming DNA loops between promoters and enhancers in a cell type-specific fashion. Thus, our findings of increased expression of these factors in liver of MLP offspring implicate a possible novel epigenetic mechanism in developmental programming.
    Full-text · Article · Dec 2011 · Journal of Nutrition
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    ABSTRACT: Pediatric undifferentiated soft tissue sarcomas (USTSs) are a group of malignancies composed predominantly of primitive round cell sarcomas, the histogenesis of which is uncertain. Thus, diagnosis and therapy remain a challenge. The aims of the current study were to determine whether differential expression of stem cell-associated proteins could be used to aid in determining the histogenesis of pediatric USTSs and to determine whether pediatric USTSs expressed a unique panel of stem cell-associated proteins to aid diagnosis. Tumors included 28 Ewing sarcoma/primitive neuroectodermal tumors (ESs), 22 embryonal rhabdomyosarcomas (ERMSs), 8 alveolar rhabdomyosarcomas (ARMSs), 5 synovial sarcomas (SSs), 5 malignant peripheral nerve sheath tumors (MPNSTs), and 13 USTSs. Stem cell antibodies included 3 mesenchymal stem cell markers (CD44, CD105, and CD166) and 5 neural stem cell markers (CD15, CD29, CD56, CD133, and nestin). Sections were scored followed by statistical analysis, clustering analysis, and visualizations using Partek Genomic Suite Software. The Euclidean clustering divided the tumors into 2 major groups. ESs and USTSs formed the majority of the 1st group, whereas ERMSs, ARMSs, MPNSTs, and SSs formed the 2nd group. Reduced expression of CD56 was strongly associated with the ES/USTS cluster (P < 0.0001). ESs and USTSs were further separated by CD166 staining, wherein increased expression was associated with ES (P < 0.0001). The 2nd group included the majority of other sarcomas, with no consistent separation between subtypes. The current study demonstrates the usefulness of applying stem cell markers to pediatric sarcomas and indicates that USTSs and ESs are closely related and may share a common histogenesis.
    No preview · Article · Jan 2011 · Pediatric and Developmental Pathology
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    Dataset: Figure S2
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    ABSTRACT: Analysis of sequence homology at mtDNA deletion breakpoints. The two breakpoints in each mtDNA deletion sample (Prox. and Dist. Ref.) were aligned using ClustalW alignment tool. Alignments were grouped based on the location of the breakpoint as either within a direct repeat sequence (type I), or not within a direct repeat sequence (type II). Direct repeats of 5+ nucleotides are highlighted (dark grey), and repeats of smaller size are highlighted (light gray). Mapped breakpoint nucleotides are in red. ClustalW alignments where the breakpoints do not align (in Type II breakpoints) are because, ClustalW alignment shifts the alignment to achieve maximum homology in that region. Top strand in each alignment is the proximal breakpoint sequence and bottom is the distal breakpoint sequence from Table S1. Alignments corresponding to the individual patient case from Table S1 are indicated to the left of the alignment. (TIFF)
    Preview · Dataset · Dec 2010
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    Dataset: Table S1
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    ABSTRACT: The “breakpoint nucleotide” refers to the nucleotide position at which the breakpoint has occurred, either in the 5′ or the 3′ position. A majority of the subjects analyzed have either a single nucleotide, or a stretch of identical nucleotides (direct repeats), present at the two breakpoints flanking the deletion. As such, the sequence alignment of the breakpoints does not allow us to predict if the breakpoint happens at the 5′ or the 3′ of the overlapping nucleotide/s at the breakpoint 1 and 2 respectively. We refer to the common region of overlap as the “breakpoint nucleotide”. The breakpoint nucleotide is indicated in columns proximal breakpoint reference sequence (5′ to 3′) and distal breakpoint sequence (5′ to 3′) with “[]”. In cases with direct repeats at breakpoints, which are longer than 1 nucleotide, the most 5′ nucleotide of the direct repeat is indicated with the bracket. These correspond to the nucleotides that are labeled in red color in Figure 3 and Figure S2. The sequences in the Proximal breakpoint reference sequence column which are 3′ from the breakpoint nucleotide, and sequences in the Distal breakpoint sequence column which are 5′ from the breakpoint nucleotide represent the 5′ and 3′ sequences of the deleted molecule respectively. In cases where there is not a common nucleotide(s) at the two breakpoints, the sequence breakpoint is predicted to be 3′ to the breakpoint nucleotide in the breakpoint 1 sequence, and 5′ to the breakpoint nucleotide in the breakpoint 2 sequence. All sequences are presented in 5′ to 3′ direction, left to right. (XLSX)
    Preview · Dataset · Dec 2010
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    Dataset: Figure S1
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    ABSTRACT: Mapping of mtDNA breakpoints. A) The position of the mtDNA deletion and level of heteroplasmy was determined using the clinical MitoMet array using a previously published protocol [18]. Y-axis shows the position of the probes along the mitochondrial chromosome. The location and the level of heteroplasmy was calculated based on normalized probe intensity to age and tissue matched controls. B) Based on the MitoMet results mtDNA was PCR amplified and sequenced across the breakpoint to determine the precise nucleotides involved in the breakpoint. Top sequence represents sequence 5′ to the breakpoint and bottom sequence represents the sequence 3′ to the breakpoint. Middle sequence is sequence across the patient's breakpoint (TIFF)
    Preview · Dataset · Dec 2010
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    ABSTRACT: Mitochondrial DNA (mtDNA) deletions are a common cause of mitochondrial disorders. Large mtDNA deletions can lead to a broad spectrum of clinical features with different age of onset, ranging from mild mitochondrial myopathies (MM), progressive external ophthalmoplegia (PEO), and Kearns-Sayre syndrome (KSS), to severe Pearson syndrome. The aim of this study is to investigate the molecular signatures surrounding the deletion breakpoints and their association with the clinical phenotype and age at onset. MtDNA deletions in 67 patients were characterized using array comparative genomic hybridization (aCGH) followed by PCR-sequencing of the deletion junctions. Sequence homology including both perfect and imperfect short repeats flanking the deletion regions were analyzed and correlated with clinical features and patients' age group. In all age groups, there was a significant increase in sequence homology flanking the deletion compared to mtDNA background. The youngest patient group (<6 years old) showed a diffused pattern of deletion distribution in size and locations, with a significantly lower sequence homology flanking the deletion, and the highest percentage of deletion mutant heteroplasmy. The older age groups showed rather discrete pattern of deletions with 44% of all patients over 6 years old carrying the most common 5 kb mtDNA deletion, which was found mostly in muscle specimens (22/41). Only 15% (3/20) of the young patients (<6 years old) carry the 5 kb common deletion, which is usually present in blood rather than muscle. This group of patients predominantly (16 out of 17) exhibit multisystem disorder and/or Pearson syndrome, while older patients had predominantly neuromuscular manifestations including KSS, PEO, and MM. In conclusion, sequence homology at the deletion flanking regions is a consistent feature of mtDNA deletions. Decreased levels of sequence homology and increased levels of deletion mutant heteroplasmy appear to correlate with earlier onset and more severe disease with multisystem involvement.
    Full-text · Article · Dec 2010 · PLoS ONE
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    ABSTRACT: Human osteosarcoma is the most common pediatric bone tumor. There is limited understanding of the molecular mechanisms underlying osteosarcoma oncogenesis, and a lack of good diagnostic as well as prognostic clinical markers for this disease. Recent discoveries have highlighted a potential role of a number of genes including: RECQL4, DOCK5, SPP1, RUNX2, RB1, CDKN1A, P53, IBSP, LSAMP, MYC, TNFRSF1B, BMP2, HISTH2BE, FOS, CCNB1, and CDC5L. Our objective was to assess relative expression levels of these 16 genes as potential biomarkers of osteosarcoma oncogenesis and chemotherapy response in human tumors. We performed quantitative expression analysis in a panel of 22 human osteosarcoma tumors with differential response to chemotherapy, and 5 normal human osteoblasts. RECQL4, SPP1, RUNX2, and IBSP were significantly overexpressed, and DOCK5, CDKN1A, RB1, P53, and LSAMP showed significant loss of expression relative to normal osteoblasts. In addition to being overexpressed in osteosarcoma tumor samples relative to normal osteoblasts, RUNX2 was the only gene of the 16 to show significant overexpression in tumors that had a poor response to chemotherapy relative to good responders. These data underscore the loss of tumor suppressive pathways and activation of specific oncogenic mechanisms associated with osteosarcoma oncogenesis, while drawing attention to the role of RUNX2 expression as a potential biomarker of chemotherapy failure in osteosarcoma.
    Full-text · Article · May 2010 · BMC Cancer

Publication Stats

752 Citations
124.92 Total Impact Points

Institutions

  • 2015
    • Western University
      London, Ontario, Canada
  • 2013-2015
    • McMaster University
      • Department of Pathology and Molecular Medicine
      Hamilton, Ontario, Canada
  • 2010-2013
    • Baylor College of Medicine
      • Department of Molecular & Human Genetics
      Houston, TX, United States
  • 2008-2010
    • SickKids
      • Program in Genetics and Genome Biology
      Toronto, Ontario, Canada
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
  • 2004-2008
    • The University of Western Ontario
      London, Ontario, Canada
  • 2006
    • London Health Sciences Centre
      • Department of Pathology
      London, Ontario, Canada