Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 54
Filter
1.
Virchows Arch ; 471(4): 491-500, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28812131

ABSTRACT

Formalin-fixed paraffin-embedded (FFPE) tissue blocks are widely used to identify clinically actionable molecular alterations or perform retrospective molecular studies. Our goal was to quantify degradation of DNA occurring during mid to long-term storage of samples in usual conditions. We selected 46 FFPE samples of surgically resected carcinomas of lung, colon, and urothelial tract, of which DNA had been previously extracted. We performed a second DNA extraction on the same blocks under identical conditions after a median period of storage of 5.5 years. Quantitation of DNA by fluorimetry showed a 53% decrease in DNA quantity after storage. Quantitative PCR (qPCR) targeting KRAS exon 2 showed delayed amplification of DNA extracted after storage in all samples but one. The qPCR/fluorimetry quantification ratio decreased from 56 to 15% after storage (p < 0.001). Overall, remaining proportion of DNA analyzable by qPCR represented only 11% of the amount obtained at first extraction. Maximal length of amplifiable DNA fragments assessed with a multiplex PCR was reduced in DNA extracted from stored tissue, indicating that DNA fragmentation had increased in the paraffin blocks during storage. Next-generation sequencing was performed on 12 samples and showed a mean 3.3-fold decrease in library yield and a mean 4.5-fold increase in the number of single-nucleotide variants detected after storage. In conclusion, we observed significant degradation of DNA extracted from the same FFPE block after 4 to 6 years of storage. Better preservation strategies should be considered for storage of FFPE biopsy specimens.


Subject(s)
DNA/analysis , Tissue Fixation , Carcinoma/genetics , Formaldehyde , High-Throughput Nucleotide Sequencing , Humans , Paraffin Embedding , Real-Time Polymerase Chain Reaction , Retrospective Studies
2.
J Exp Med ; 212(6): 939-51, 2015 Jun 01.
Article in English | MEDLINE | ID: mdl-26008899

ABSTRACT

Inherited, complete deficiency of human HOIL-1, a component of the linear ubiquitination chain assembly complex (LUBAC), underlies autoinflammation, infections, and amylopectinosis. We report the clinical description and molecular analysis of a novel inherited disorder of the human LUBAC complex. A patient with multiorgan autoinflammation, combined immunodeficiency, subclinical amylopectinosis, and systemic lymphangiectasia, is homozygous for a mutation in HOIP, the gene encoding the catalytic component of LUBAC. The missense allele (L72P, in the PUB domain) is at least severely hypomorphic, as it impairs HOIP expression and destabilizes the whole LUBAC complex. Linear ubiquitination and NF-κB activation are impaired in the patient's fibroblasts stimulated by IL-1ß or TNF. In contrast, the patient's monocytes respond to IL-1ß more vigorously than control monocytes. However, the activation and differentiation of the patient's B cells are impaired in response to CD40 engagement. These cellular and clinical phenotypes largely overlap those of HOIL-1-deficient patients. Clinical differences between HOIL-1- and HOIP-mutated patients may result from differences between the mutations, the loci, or other factors. Our findings show that human HOIP is essential for the assembly and function of LUBAC and for various processes governing inflammation and immunity in both hematopoietic and nonhematopoietic cells.


Subject(s)
Gene Expression Regulation , Ubiquitin-Protein Ligases/deficiency , Alleles , Amino Acid Sequence , CD40 Ligand/metabolism , Catalysis , Female , Fibroblasts/metabolism , Genetic Complementation Test , Germ-Line Mutation , Glycogen Storage Disease Type IV/pathology , Homozygote , Humans , Immunologic Deficiency Syndromes/pathology , Inflammation , Lymphangiectasis/pathology , Monocytes/metabolism , Mutation, Missense , NF-kappa B/metabolism , Sequence Homology, Amino Acid , Transcription Factors , Ubiquitin/chemistry , Ubiquitin-Protein Ligases/genetics , Young Adult
3.
Pediatr Surg Int ; 31(4): 375-9, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25652760

ABSTRACT

Congenital/infantile fibrosarcoma (IFS) is a relatively rare form of fibrosarcoma diagnosed at birth or during early years of life and that differs from its adult counterpart because of a more favorable behavior. IFS is also known as cellular congenital mesoblastic nephroma, when it affects the kidney and is often but not always characterized by the ETV6-NTRK3 fusion transcript. We report herein the first series of an exceptional tumor of the small intestine occurring in newborns. The four patients shared a stereotyped clinico-pathological presentation with early and acute onset, intestinal perforation, and an infiltration by a highly cellular spindle cell tumor within the dilated intestinal wall exhibiting pathologic features typical of IFS. Molecular studies for the ETV6-NTRK3 translocation were negative in the three cases tested. Patients were treated by surgical wide resection alone and are alive and well (follow-up: 36 months-25 years). Thus, this new clinico-pathological entity, even with lack of documented evidence of the ETV6-NTRK3 translocation, should be included in the differential diagnosis of congenital bowel perforation or obstruction and may represent an intestinal counterpart of IFS.


Subject(s)
Fibrosarcoma/congenital , Intestinal Neoplasms/congenital , Intestine, Small/pathology , Diagnosis, Differential , Female , Fibrosarcoma/pathology , Humans , Infant , Infant, Newborn , Intestinal Neoplasms/pathology , Male
4.
J Pediatr Hematol Oncol ; 37(2): e118-20, 2015 Mar.
Article in English | MEDLINE | ID: mdl-24390443

ABSTRACT

An 8-month-old girl underwent surgical resection of a cervical mass with histologic diagnosis of a primitive myxoid mesenchymal tumor of infancy (PMMTI). More than 5 years after the initial surgical intervention, the tumor recurred locally, with numerous distant metastases. The histologic morphology of this tumor was compatible with a diagnosis of an undifferentiated high-grade sarcoma. PMMTI is a recently described poorly differentiated fibroblastic soft-tissue tumor of infancy, of at least borderline biological behavior, characterized by local recurrence and a potential to metastasize. We present here the first case of a transformation of a PMMTI into an undifferentiated high-grade sarcoma.


Subject(s)
Cell Differentiation , Mesenchymoma/pathology , Neoplasm Recurrence, Local/pathology , Sarcoma/secondary , Soft Tissue Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Humans , Infant , Mesenchymoma/drug therapy , Neoplasm Recurrence, Local/drug therapy , Prognosis , Sarcoma/drug therapy , Soft Tissue Neoplasms/drug therapy
5.
Toxicol Sci ; 137(1): 114-24, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24154488

ABSTRACT

The contribution of environmental pollutants to liver fibrosis is an important and poorly explored issue. In vitro studies suggest that the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other aryl hydrocarbon receptor (AhR) ligands induce several genes that are known to be upregulated during liver fibrosis. Our aim was to determine whether exposure to such pollutants can lead to liver fibrosis and to characterize the mechanisms of action. Mice were treated for 2, 14, or 42 days, once a week with 25 µg/kg of TCDD. Gene and protein expression, in vitro and in vivo, as well as liver histology were investigated for each treatment. Treatment of mice with TCDD for 2 weeks modified the hepatic expression of markers of fibrosis such as collagen 1A1 and α-smooth muscle actin. This is not observed in AhR knockout mice. Following 6 weeks of treatment, histological features of murine hepatic fibrosis became apparent. In parallel, the levels of inflammatory cytokines (interleukin-1 beta, tumor necrosis factor α) and of markers of activated fibroblasts(fibroblast-specific protein 1) were found to be upregulated. Interestingly, we also found increased expression of genes of the TGF-ß pathway and a concomitant decrease of miR-200a levels. Because the transcription factors of the Snail family were shown to be involved in liver fibrosis, we studied their regulation by TCDD. Two members of the Snail family were increased, whereas their negative targets, the epithelial marker E-cadherin and Claudin 1, were decreased. Further, the expression of mesenchymal markers was increased. Finally, we confirmed that Snai2 is a direct transcriptional target of TCDD in the human hepatocarcinoma cell line, HepG2. The AhR ligand, TCDD, induces hepatic fibrosis by directly regulating profibrotic pathways.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors/agonists , Chemical and Drug Induced Liver Injury/etiology , Environmental Pollutants/toxicity , Liver Cirrhosis/chemically induced , Liver/drug effects , Polychlorinated Dibenzodioxins/toxicity , Receptors, Aryl Hydrocarbon/agonists , Animals , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Chemical and Drug Induced Liver Injury/genetics , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Dose-Response Relationship, Drug , Epithelial-Mesenchymal Transition/drug effects , Gene Expression Regulation , Hep G2 Cells , Humans , Inflammation Mediators/metabolism , Ligands , Liver/metabolism , Liver/pathology , Liver Cirrhosis/genetics , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Mice , Receptors, Aryl Hydrocarbon/genetics , Receptors, Aryl Hydrocarbon/metabolism , Snail Family Transcription Factors , Time Factors , Transcription Factors/genetics , Transcription Factors/metabolism
6.
Orphanet J Rare Dis ; 8: 130, 2013 Sep 03.
Article in English | MEDLINE | ID: mdl-24004862

ABSTRACT

BACKGROUND: Type I pleuropulmonary blastoma (PPB) and congenital cystic adenomatoid malformation of the lung (CCAM) are cystic lung diseases of childhood. Their clinical and radiological presentations are often similar, and pathologic discrimination remains difficult in many cases. As a consequence, type I PPB and CCAM are frequently confused, leading to delayed adequate management for type I PPB. Recent studies have suggested a role for fibroblast growth factor (FGF) 10 signal pathway in CCAM pathogenesis. The objective of our study was to determine whether FGF10 signaling differs between CCAM and type I PPB. METHODS: Immunohistochemical studies were performed for expression of FGF10, its receptor FGFR2b, and its inhibitor sonic hedgehog (SHH) in focal type I PPB (n=6), CCAM type I (n=7), CCAM type II (n=7), and control lungs (n=5). RESULTS: FGF10, FGFR2b, and SHH expressions differed markedly between type I PPB and both types of CCAM. Type I and type II CCAM cystic walls expressed FGF10, FGFR2b, and SHH, whereas staining was absent or poor in type I PBB cystic walls. Expression of FGF10, FGFR2b, and SHH did not differ between CCAM cystic walls and control airway walls. CONCLUSIONS: These findings show that immunohistochemistry with FGF10, FGFR2b, or SHH could be useful in differentiating CCAM from type I PPB, when a child presents with a focal cystic lung lesion. The absence of strong expression of FGF10, FGFR2b, and/or SHH makes the diagnosis of CCAM very doubtful.


Subject(s)
Cystic Adenomatoid Malformation of Lung, Congenital/metabolism , Fibroblast Growth Factor 10/metabolism , Hedgehog Proteins/metabolism , Pulmonary Blastoma/metabolism , Receptor, Fibroblast Growth Factor, Type 2/metabolism , Cystic Adenomatoid Malformation of Lung, Congenital/genetics , Female , Fibroblast Growth Factor 10/genetics , Hedgehog Proteins/genetics , Humans , Immunohistochemistry , Infant , Infant, Newborn , Male , Pulmonary Blastoma/genetics , Receptor, Fibroblast Growth Factor, Type 2/genetics
7.
Am J Hum Genet ; 92(6): 1001-7, 2013 Jun 06.
Article in English | MEDLINE | ID: mdl-23731542

ABSTRACT

Infantile myofibromatosis (IM) is a disorder of mesenchymal proliferation characterized by the development of nonmetastasizing tumors in the skin, muscle, bone, and viscera. Occurrence within families across multiple generations is suggestive of an autosomal-dominant (AD) inheritance pattern, but autosomal-recessive (AR) modes of inheritance have also been proposed. We performed whole-exome sequencing (WES) in members of nine unrelated families clinically diagnosed with AD IM to identify the genetic origin of the disorder. In eight of the families, we identified one of two disease-causing mutations, c.1978C>A (p.Pro660Thr) and c.1681C>T (p.Arg561Cys), in PDGFRB. Intriguingly, one family did not have either of these PDGFRB mutations but all affected individuals had a c.4556T>C (p.Leu1519Pro) mutation in NOTCH3. Our studies suggest that mutations in PDGFRB are a cause of IM and highlight NOTCH3 as a candidate gene. Further studies of the crosstalk between PDGFRB and NOTCH pathways may offer new opportunities to identify mutations in other genes that result in IM and is a necessary first step toward understanding the mechanisms of both tumor growth and regression and its targeted treatment.


Subject(s)
Genes, Dominant , Mutation, Missense , Myofibromatosis/congenital , Receptor, Platelet-Derived Growth Factor beta/genetics , Amino Acid Sequence , Base Sequence , Female , Genetic Association Studies , Humans , Male , Myofibromatosis/genetics , Pedigree , Receptor, Notch3 , Receptors, Notch/genetics , Sequence Analysis, DNA
8.
Nat Immunol ; 13(12): 1178-86, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23104095

ABSTRACT

We report the clinical description and molecular dissection of a new fatal human inherited disorder characterized by chronic autoinflammation, invasive bacterial infections and muscular amylopectinosis. Patients from two kindreds carried biallelic loss-of-expression and loss-of-function mutations in HOIL1 (RBCK1), a component of the linear ubiquitination chain assembly complex (LUBAC). These mutations resulted in impairment of LUBAC stability. NF-κB activation in response to interleukin 1ß (IL-1ß) was compromised in the patients' fibroblasts. By contrast, the patients' mononuclear leukocytes, particularly monocytes, were hyper-responsive to IL-1ß. The consequences of human HOIL-1 and LUBAC deficiencies for IL-1ß responses thus differed between cell types, consistent with the unique association of autoinflammation and immunodeficiency in these patients. These data suggest that LUBAC regulates NF-κB-dependent IL-1ß responses differently in different cell types.


Subject(s)
Glycogen Storage Disease Type IV/genetics , Hereditary Autoinflammatory Diseases/genetics , Immunologic Deficiency Syndromes/genetics , NF-kappa B/metabolism , Ubiquitin-Protein Ligases/genetics , Bacterial Infections/genetics , Bacterial Infections/immunology , Cell Cycle Proteins/genetics , Cell Line , Fibroblasts/immunology , Fibroblasts/metabolism , Humans , Immunologic Deficiency Syndromes/metabolism , Interleukin-1beta/metabolism , Monocytes/immunology , Monocytes/metabolism , Oligonucleotide Array Sequence Analysis , Protein Serine-Threonine Kinases/antagonists & inhibitors , Protein Serine-Threonine Kinases/genetics , Repressor Proteins/genetics , Transcription Factors , Ubiquitin-Protein Ligases/deficiency , Ubiquitin-Protein Ligases/metabolism , Ubiquitination
10.
Cancer Genet ; 205(1-2): 55-60, 2012.
Article in English | MEDLINE | ID: mdl-22429598

ABSTRACT

Cytogenetic analysis of a lumbar soft tissue Ewing sarcoma (ES) in a 7-month-old female child showed a t(17;22)(q21;q12), a rare translocation leading to an EWSR1-ETV4 chimeric transcript. These findings were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) techniques. The breakpoints were characterized by direct sequencing of the chimeric fusion gene. Tumor genotyping using the Affymetrix Genome-Wide Human single nucleotide polymorphism (SNP) array 6.0 Genechip identified deletions of both chromosomal regions involved in the translocation, resulting in partial deletion of ETV4, but an uninvolved EWSR1 gene. The creation of a fusion between EWSR1 and an ETS family gene consecutive to a chromosomal translocation is characteristic of the Ewing family of tumors (EFT). This is the first report of a deletion involving the two breakpoints in an EWS-ETS translocation. To date, only two cases of t(17;22)(q21;q12) in Ewing sarcoma have been reported, with no associated deletion. Interestingly, both cases had also occurred in soft tissue tumors, which are less common than their bone-involving counterparts.


Subject(s)
Adenovirus E1A Proteins/genetics , Chromosomes, Human, Pair 17 , Chromosomes, Human, Pair 22 , Proto-Oncogene Proteins/genetics , Sarcoma, Ewing/genetics , Soft Tissue Neoplasms/genetics , Translocation, Genetic , Chromosomes, Human, Pair 17/genetics , Chromosomes, Human, Pair 22/genetics , Female , Gene Deletion , Humans , Infant , Proto-Oncogene Proteins c-ets , Sarcoma, Ewing/diagnosis , Soft Tissue Neoplasms/diagnosis
11.
Inflamm Bowel Dis ; 18(10): 1809-17, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22238154

ABSTRACT

BACKGROUND: The pathogenesis of inflammatory bowel disease (IBD) is multifactorial, with some patients presenting additional autoimmune symptoms. Inflammatory colitis associated with autoimmune (AI) liver disease appears to have clinical features different from those of "classical" ulcerative colitis (CUC). The aim of this study was to describe these features, in order to differentiate a subgroup of colitis associated with autoimmunity (CAI) from CUC. METHODS: Twenty-eight consecutive children with inflammatory colitis associated with primary sclerosing cholangitis (PSC), celiac disease, or AI hepatitis were compared with a matched control group of 27 children with isolated UC. Clinical course, histology, as well as inflammatory profile in the colonic mucosa based on real-time polymerase chain reaction (PCR) were analyzed. RESULTS: In CAI the main digestive symptoms at disease onset were abdominal pain (12/28) and bloody strings in the stool (12/28), along with a high prevalence of autoimmune diseases in relatives, as compared with bloody diarrhea in the CUC group (26/27). At diagnosis, pancolitis was seen in 18/28 CAI patients compared with 8/27 in UC. In CAI, the pathological findings were different from CUC: 1) major lesions predominantly located in the right colon; 2) pseudo-villous appearance of the mucosa, and strong infiltration with eosinophils; 3) mild glandular lesions; and 4) differing inflammatory infiltrate with reduced FOXP3, interleukin (IL)-2, and thymic stromal lymphopoietin (TSLP) levels. Evolution in CAI was less aggressive, requiring less corticosteroids/immunomodulators. CONCLUSIONS: Precise clinical, histological, and molecular analyses reveal marked differences between patients with CUC and those with associated AI phenomena, supporting the hypothesis of a distinct AI presentation of IBD.


Subject(s)
Autoimmune Diseases/etiology , Colitis, Ulcerative/complications , Liver Diseases/etiology , Adolescent , Autoantibodies/blood , Autoimmune Diseases/pathology , Case-Control Studies , Child , Child, Preschool , Colitis, Ulcerative/pathology , Female , Humans , Infant , Liver Diseases/pathology , Male , Prognosis , Retrospective Studies
12.
Pediatr Transplant ; 16(5): E146-9, 2012 Aug.
Article in English | MEDLINE | ID: mdl-21395954

ABSTRACT

PAP is a rare alveolointerstitial lung disorder characterized histologically by the intra-alveolar accumulation of eosinophilic and PAS-positive material. We observed two cases of PAP after unrelated CB hematopoietic progenitor cell transplantation in children with ALL. No antagonist activity toward GM-CSF was identified in the patient tested. The putative multifactorial PAP etiology is discussed. This potentially curable condition should be considered in a CB allograft recipient with alveolointerstial lung disorder.


Subject(s)
Cord Blood Stem Cell Transplantation , Hematopoietic Stem Cell Transplantation , Postoperative Complications/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/surgery , Pulmonary Alveolar Proteinosis/diagnosis , Adolescent , Child, Preschool , Fatal Outcome , Female , Humans , Male , Postoperative Complications/etiology , Pulmonary Alveolar Proteinosis/etiology
13.
Orphanet J Rare Dis ; 6: 63, 2011 Oct 03.
Article in English | MEDLINE | ID: mdl-21967988

ABSTRACT

Congenital hyperinsulinism (HI) is an inappropriate insulin secretion by the pancreatic ß-cells secondary to various genetic disorders. The incidence is estimated at 1/50, 000 live births, but it may be as high as 1/2, 500 in countries with substantial consanguinity. Recurrent episodes of hyperinsulinemic hypoglycemia may expose to high risk of brain damage. Hypoglycemias are diagnosed because of seizures, a faint, or any other neurological symptom, in the neonatal period or later, usually within the first two years of life. After the neonatal period, the patient can present the typical clinical features of a hypoglycemia: pallor, sweat and tachycardia. HI is a heterogeneous disorder with two main clinically indistinguishable histopathological lesions: diffuse and focal. Atypical lesions are under characterization. Recessive ABCC8 mutations (encoding SUR1, subunit of a potassium channel) and, more rarely, recessive KCNJ11 (encoding Kir6.2, subunit of the same potassium channel) mutations, are responsible for most severe diazoxide-unresponsive HI. Focal HI, also diazoxide-unresponsive, is due to the combination of a paternally-inherited ABCC8 or KCNJ11 mutation and a paternal isodisomy of the 11p15 region, which is specific to the islets cells within the focal lesion. Genetics and 18F-fluoro-L-DOPA positron emission tomography (PET) help to diagnose diffuse or focal forms of HI. Hypoglycemias must be rapidly and intensively treated to prevent severe and irreversible brain damage. This includes a glucose load and/or a glucagon injection, at the time of hypoglycemia, to correct it. Then a treatment to prevent the recurrence of hypoglycemia must be set, which may include frequent and glucose-enriched feeding, diazoxide and octreotide. When medical and dietary therapies are ineffective, or when a focal HI is suspected, surgical treatment is required. Focal HI may be definitively cured when the partial pancreatectomy removes the whole lesion. By contrast, the long-term outcome of diffuse HI after subtotal pancreatectomy is characterized by a high risk of diabetes, but the time of its onset is hardly predictable.


Subject(s)
Congenital Hyperinsulinism/diagnosis , Congenital Hyperinsulinism/therapy , Child , Child, Preschool , Congenital Hyperinsulinism/genetics , Congenital Hyperinsulinism/physiopathology , Fluorine Radioisotopes , Humans , Infant , Infant, Newborn , Levodopa , Positron-Emission Tomography
16.
Pediatr Dev Pathol ; 13(1): 66-71, 2010.
Article in English | MEDLINE | ID: mdl-19425818

ABSTRACT

Females with 46,XY complete gonadal dysgenesis are at significant risk of developing germ cell tumors, mostly gonadoblastomas. We present here the case of 2 half-sisters, sharing the same father, diagnosed with 46,XY complete gonadal dysgenesis. The 1st sister developed a gonadoblastoma and an invasive dysgerminoma, whereas the 2nd sister developed a gonadoblastoma and an invasive choriocarcinoma within the same gonad. No SRY mutation, chromosome abnormalities, or mosaicism were detected in blood. Single nucleotide polymorphism (SNP) profiling of the choriocarcinoma revealed a complex hyperdiploid pattern with gains of 1 to 4 copies of material from several autosomes, as well as the loss of the Y chromosome and a homozygous SNP profile without copy number change for the X chromosome. Our results are in agreement with the recurrent chromosome gains and losses previously published in germ cell tumors, and the coexistence of both tumors within the same gonad suggests that choriocarcinomas may derive from gonadoblastomas.


Subject(s)
Choriocarcinoma, Non-gestational/genetics , Dysgerminoma/genetics , Gonadal Dysgenesis, 46,XY/genetics , Gonadoblastoma/genetics , Neoplasms, Multiple Primary , Polymorphism, Single Nucleotide , Uterine Neoplasms/genetics , Adolescent , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant , Child , Choriocarcinoma, Non-gestational/pathology , Choriocarcinoma, Non-gestational/therapy , Chromosome Deletion , Chromosomes, Human, Y , Dysgerminoma/pathology , Dysgerminoma/therapy , Fatal Outcome , Female , Gonadal Dysgenesis, 46,XY/pathology , Gonadal Dysgenesis, 46,XY/therapy , Gonadoblastoma/pathology , Gonadoblastoma/therapy , Humans , In Situ Hybridization, Fluorescence , Oligonucleotide Array Sequence Analysis , Siblings , Spectral Karyotyping , Uterine Neoplasms/pathology , Uterine Neoplasms/therapy , Young Adult
17.
Hum Pathol ; 40(9): 1347-52, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19454362

ABSTRACT

Since the first description of sclerosing rhabdomyosarcoma in 2000, 19 pediatric cases have been reported in the literature. However, it is debated whether sclerosing rhabdomyosarcoma represents a specific rhabdomyosarcoma entity or a variant of embryonal or alveolar rhabdomyosarcoma. To date, 6 sclerosing rhabdomyosarcoma karyotypes and 1 sclerosing rhabdomyosarcoma comparative genomic hybridization profile have been reported. We present the first whole-genome tumoral genotyping of a sclerosing rhabdomyosarcoma by high-density single nucleotide polymorphism array. The single nucleotide polymorphism genotyping revealed a complex pattern including gains and losses of whole chromosomes and an amplification of the 12q13-15 region. Amplification of the 12q13-q15 region containing SAS, GLI, CDK4, and MDM2 has been observed in rhabdomyosarcoma. In the present case, the 2 amplified target genes were MDM2 and HMGA2, excluding CDK4. The identification of a specific MDM2-HGMA2 amplicon excluding CDK4 has only been described so far in well-differentiated and dedifferentiated liposarcoma. Further studies are needed to assess if this anomaly is a specific marker of sclerosing rhabdomyosarcoma.


Subject(s)
Aneuploidy , HMGA2 Protein/genetics , Polymorphism, Single Nucleotide , Proto-Oncogene Proteins c-mdm2/genetics , Rhabdomyosarcoma/genetics , Child , Humans , In Situ Hybridization, Fluorescence , Male , Nucleic Acid Amplification Techniques
19.
Pediatr Dev Pathol ; 12(5): 371-3, 2009.
Article in English | MEDLINE | ID: mdl-19222307

ABSTRACT

Involvement of the Wnt signal transduction pathway has been shown in different pediatric embryonal tumors, such as hepatoblastoma, nephroblastoma, pancreatoblastoma, and medulloblastoma. There are few data available on the status of beta-catenin in rhabdomyosarcoma (RMS), another pediatric embryonal tumor. The aims of this study were 1st to verify the status of the exon 3 of CTNNB1 and 2nd to assess the usefulness of beta-catenin immunostaining in a small series of 8 embryonal RMS, 3 alveolar RMS, and 1 sclerosing RMS (SRMS). Sequence analysis revealed no mutations in the exon 3 of CTNNB1 in all the tumors studied. All RMS showed a cytoplasmic beta-catenin staining with cytoplasmic membrane reinforcement and no nuclear delocalization. We conclude that there is no evidence of beta-catenin mutation in the genesis of rhabdomyosarcoma and that beta-catenin does not represent a useful immunomarker to help distinguish between embryonal RMS and alveolar RMS.


Subject(s)
Rhabdomyosarcoma, Alveolar/genetics , Rhabdomyosarcoma, Alveolar/pathology , Rhabdomyosarcoma, Embryonal/genetics , Rhabdomyosarcoma, Embryonal/pathology , beta Catenin/genetics , Adolescent , Biomarkers, Tumor/genetics , Child , Child, Preschool , Female , Humans , Immunohistochemistry , Infant , Male , Mutation , Polymerase Chain Reaction
20.
Pediatr Dev Pathol ; 12(5): 390-3, 2009.
Article in English | MEDLINE | ID: mdl-19192951

ABSTRACT

Community-associated infections and especially pleural empyema due to Staphylococcus aureus are increasing worldwide. The virulence of staphylococcal strains is notably determined by different toxin expressing-genes, such as the Panton-Valentine leukocidin (PVL) gene found in S. aureus isolates obtained from pediatric necrotizing pneumonia samples. We describe 2 similar cases of infants with severe respiratory distress and death after an upper respiratory tract infection, having occurred in the same urban area during the same winter time. Necropsies performed between November 2006 and March 2007 revealed bronchopneumonia and an important pleural empyema, justifying the review of clinical charts and laboratory exams. A methicillin-sensitive S. aureus (MSSA) isolate carrying the PVL gene was identified in both cases. We have subsequently cared for an additional case in the same time interval with sudden death and similar pathological findings. No positive microbiological results were obtained, a negative finding possibly related to a 5-day antibiotics regimen. This report describes the pathological features of these cases and stresses the need to recognize PVL-positive S. aureus infections in young children. Finally, we believe that all lethal infections due to PVL-positive S. aureus, independently of the methicillin resistance profile, deserve a mandatory report to the provincial public health authorities.


Subject(s)
Empyema, Pleural/microbiology , Empyema, Pleural/pathology , Staphylococcal Infections/microbiology , Staphylococcal Infections/pathology , Empyema, Pleural/physiopathology , Fatal Outcome , Female , Humans , Infant , Infant, Newborn , Male , Staphylococcal Infections/physiopathology , Staphylococcus aureus
SELECTION OF CITATIONS
SEARCH DETAIL
...