Dorothée Bouron-Dal Soglio

CHU Sainte-Justine, Montréal, Quebec, Canada

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Publications (31)112.81 Total impact

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    ABSTRACT: Embryonal rhabdomyosarcoma (ERMS), a soft tissue sarcoma, is one of the most common pediatric cancers. Certain ERMSs are associated with the DICER1 syndrome, a tumor predisposition syndrome caused by germ-line DICER1 mutations. Characteristic somatic mutations have also been identified in DICER1-associated tumor types. These "hotspot" mutations affect the catalytic activity of the DICER1 ribonuclease IIIb domain. Primary ovarian ERMS (oERMS) is extremely rare. We present a case of a 6-year-old girl with an oERMS harboring 2 DICER1 mutations. The girl also exhibited other DICER1 phenotypes: cystic nephroma (CN) and multinodular goiter. Somatic investigations of the CN identified a hotspot DICER1 mutation different from that in the oERMS. Significantly, the CN presented at 12 years of age, which is much older than the previously reported age range of susceptibility. This report documents the occurrence of DICER1 mutations in a case of oERMS, expanding the spectrum of DICER1-associated tumors. Copyright © 2015. Published by Elsevier Inc.
    Human pathology 03/2015; DOI:10.1016/j.humpath.2015.02.008 · 2.81 Impact Factor
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    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.
    Pediatric Surgery International 02/2015; 31(4). DOI:10.1007/s00383-015-3670-7 · 1.06 Impact Factor
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    ABSTRACT: Germ-line RB-1 mutations predispose to pineoblastoma (PinB), but other predisposing genetic factors are not well established. We recently identified a germ-line DICER1 mutation in a child with a PinB. This was accompanied by loss of heterozygosity (LOH) of the wild-type allele within the tumour. We set out to establish the prevalence of DICER1 mutations in an opportunistically ascertained series of PinBs. Twenty-one PinB cases were studied: Eighteen cases had not undergone previous testing for DICER1 mutations; three patients were known carriers of germ-line DICER1 mutations. The eighteen PinBs were sequenced by Sanger and/or Fluidigm-based next-generation sequencing to identify DICER1 mutations in blood gDNA and/or tumour gDNA. Testing for somatic DICER1 mutations was also conducted on one case with a known germ-line DICER1 mutation. From the eighteen PinBs, we identified four deleterious DICER1 mutations, three of which were germ line in origin, and one for which a germ line versus somatic origin could not be determined; in all four, the second allele was also inactivated leading to complete loss of DICER1 protein. No somatic DICER1 RNase IIIb mutations were identified. One PinB arising in a germ-line DICER1 mutation carrier was found to have LOH. This study suggests that germ-line DICER1 mutations make a clinically significant contribution to PinB, establishing DICER1 as an important susceptibility gene for PinB and demonstrates PinB to be a manifestation of a germ-line DICER1 mutation. The means by which the second allele is inactivated may differ from other DICER1-related tumours.
    Acta Neuropathologica 07/2014; 128(4). DOI:10.1007/s00401-014-1318-7 · 9.78 Impact Factor
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    ABSTRACT: Objectives: To study and compare the effectiveness of p16(INK4a) staining and specific human papillomavirus (HPV) subtypes as a prognostic marker in cervical intraepithelial neoplasia grade 1 (CIN1; low-grade squamous intraepithelial lesions). Methods: Sixty-four cervical samples diagnosed as CIN1 and stained with p16(INK4a), with HPV status assessed by polymerase chain reaction direct sequencing. Results: Of the 34 p16(INK4a)-negative biopsy specimens, 26 regressed, seven persisted, and one progressed Of the 20 p16(INK4a) diffusely positive biopsy specimens, seven regressed, eight persisted, and five progressed. Ten biopsy specimens stained positive only in the lower one-third of the sample, of which seven regressed and three persisted p16(INK4a) diffusely positive CIN1 lesions were associated with only high-risk HPV subtypes, with the exception of one HPV-negative biopsy specimen. Three different high-risk HPV subtypes and one low-risk HPV subtype (HPV66) were identified in the six CIN1 lesions that progressed Conclusions: There is a significant relationship between p16(INK4a) immunostaining and follow-up (P = .002). p16(INK4a)-negative specimens or positivity in the lower one-third of CIN1 lesions seldom progress to a CIN2-3 lesion.
    American Journal of Clinical Pathology 07/2014; 142(1):104-10. DOI:10.1309/AJCPBX74QXCPXIKK · 3.01 Impact Factor
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    ABSTRACT: Carriers of germ-line DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 Syndrome. Thyroid abnormalities are a common finding in DICER1 syndrome with multinodular goitre (MNG) frequently present in many families in which a germ-line DICER1 mutation is segregating. Differentiated thyroid carcinoma (DTC) is infrequently seen in such pedigrees. In addition to germ-line DICER1 mutations, specific somatic mutations have been identified in the DICER1 RNase IIIb catalytic domain in several tumour types. We aimed to determine whether such characteristic somatic DICER1 mutations are present in DTCs that arise within germ-line-DICER1 mutation carriers. The study involved an opportunistic collection of three cases of DTC arising in individuals suspected to have DICER1 syndrome. Hospital-based ascertainment and testing. We identified somatic DICER1 mutations in three DTCs arising in unrelated germ-line DICER1 mutation carriers, all of whom had been diagnosed in infancy with pleuropulmonary blastoma (PPB), were treated with chemotherapy, exposed frequently to diagnostic radiation and subsequently developed DTC. The somatic mutations occurred within the DICER1 RNase IIIb domain, affecting highly conserved amino acid residues central to the catalytic activity of the domain. This report of somatic DICER1 mutations in DTC strengthens the association between DTC and the DICER1 syndrome. The possible association between germ-line DICER1 mutations, PPB treatment and the risk of subsequent DTC must be considered by clinicians when treating PPB. Exploring the association between DICER1 mutations and differentiated thyroid carcinoma.
    The Journal of Clinical Endocrinology and Metabolism 03/2014; 99(6):jc20134206. DOI:10.1210/jc.2013-4206 · 6.31 Impact Factor
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    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.
    Journal of Pediatric Hematology/Oncology 01/2014; DOI:10.1097/MPH.0000000000000107 · 0.96 Impact Factor
  • Pediatric Blood & Cancer 07/2013; 60(12). DOI:10.1002/pbc.24692 · 2.56 Impact Factor
  • Melanie I Morris, Dorothée Bouron-Dal Soglio, Alain Ouimet, Ann Aspirot, Natalie Patey
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    ABSTRACT: INTRODUCTION: Calretinin, a calcium-binding protein, has been reported to be an important new marker in Hirschsprung's disease (HD). The aim is to study the diagnostic value of Calretinin in total colonic aganglionosis (TA), prematurity, and superficial biopsy when nerve hyperplasia may not be accessed by ACE activity. METHODS: Records of patients diagnosed with HD at our institution from 1985 to 2010 were studied and patients with TA identified. We examined tissue samples from those TA, partial colectomies for HD, biopsies for suspicion of HD, and rectal tissue from aborted fetuses. Immunohistochemical analysis of Calretinin was compared with ACE gold standard method in all cases. RESULTS: In the majority of the cases, the diagnosis was ascertained by ACE activity and Calretinin staining. However, in 9 cases, the diagnosis was possible with Calretinin staining but not with ACE: in 4 TA because of the absence of nerve hyperplasia, and in 5 cases because the biopsies were too superficial to examine the nerve hyperplasia. In addition, Calretinin was expressed in the gut as early as 22 gestational weeks. CONCLUSION: The use of Calretinin staining may be superior to ACE activity, particularly in the context of TA, superficial biopsies, and prematurity, allowing earlier diagnosis.
    Journal of Pediatric Surgery 05/2013; 48(5):1037-1043. DOI:10.1016/j.jpedsurg.2013.02.026 · 1.31 Impact Factor
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    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.
    Cancer Genetics 01/2012; 205(1-2):55-60. DOI:10.1016/j.cancergen.2012.01.007 · 2.42 Impact Factor
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    ABSTRACT: DICER1 is crucial for embryogenesis and early development. Forty different heterozygous germline DICER1 mutations have been reported worldwide in 42 probands that developed as children or young adults, pleuropulmonary blastoma (PPB), cystic nephroma (CN), ovarian sex cord-stromal tumors (especially Sertoli-Leydig cell tumor [SLCT]), and/or multinodular goiter (MNG). We report DICER1 mutations in seven additional families that manifested uterine cervix embryonal rhabdomyosarcoma (cERMS, four cases) and primitive neuroectodermal tumor (cPNET, one case), Wilms tumor (WT, three cases), pulmonary sequestration (PS, one case), and juvenile intestinal polyp (one case). One carrier developed (age 25 years) a pleomorphic sarcoma of the thigh; another carrier had transposition of great arteries (TGA). These observations show that cERMS, cPNET, WT, PS, and juvenile polyps fall within the spectrum of DICER1-related diseases. DICER1 appears to be the first gene implicated in the etiology of cERMS, cPNET, and PS. Young adulthood sarcomas and perhaps congenital malformations such as TGA may also be associated.
    Human Mutation 12/2011; 32(12):1381-4. DOI:10.1002/humu.21600 · 5.05 Impact Factor
  • J Rebeuh, S Willot, D. Bouron-Dal Soglio, N Patey, D Herzog, C Faure
    Endoscopy 07/2011; 43 Suppl 2 UCTN:E256. DOI:10.1055/s-0030-1256519 · 5.20 Impact Factor
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    ABSTRACT: Nontoxic multinodular goiter (MNG) is frequently observed in the general population, but little is known about the underlying genetic susceptibility to this disease. Familial cases of MNG have been reported, and published reports describe 5 families that also contain at least 1 individual with a Sertoli-Leydig cell tumor of the ovary (SLCT). Germline mutations in DICER1, a gene that codes for an RNase III endoribonuclease, have been identified in families affected by pleuropulmonary blastoma (PPB), some of whom include cases of MNG and gonadal tumors such as SLCTs. To determine whether familial MNG with or without SLCT in the absence of PPB was associated with mutations in DICER1. From September 2009 to September 2010, we screened 53 individuals from 2 MNG and 3 MNG/SLCT families at McGill University for mutations in DICER1. We investigated blood lymphocytes and MNG and SLCT tissue from family members for loss of the wild-type DICER1 allele (loss of heterozygosity), DICER1 expression, and microRNA (miRNA) dysregulation. Detection of germline DICER1 gene mutations in familial MNG with and without SLCT. We identified and characterized germline DICER1 mutations in 37 individuals from 5 families. Two mutations were predicted to be protein truncating, 2 resulted in in-frame deletions, and 1 was a missense mutation. Molecular analysis of the 3 SLCTs showed no loss of heterozygosity of DICER1, and immunohistochemical analysis in 2 samples showed strong expression of DICER1 in Sertoli cells but weak staining of Leydig cells. miRNA profiling of RNA from lymphoblastoid cell lines from both affected and unaffected members of the familial MNG cases revealed miRNA perturbations in DICER1 mutation carriers. DICER1 mutations are associated with both familial MNG and MNG with SLCT, independent of PPB. These germline DICER1 mutations are associated with dysregulation of miRNA expression patterns.
    JAMA The Journal of the American Medical Association 01/2011; 305(1):68-77. DOI:10.1001/jama.2010.1910 · 30.39 Impact Factor
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    ABSTRACT: Multilocular cystic nephroma (CN) is a benign kidney tumour and is part of a family of kidney neoplasms including cystic partially differentiated nephroblastoma and Wilms tumour (WT). CN is rarely familial or bilateral, but it occurs in about 10% of families where pleuropulmonary blastoma (PPB) is present. Recently, germline mutations in DICER1 were found in familial PPB. To search for DICER1 mutations in two families with familial CN; PPB was present in one family. Additionally, to test germline DNA from 50 children with sporadic WT for DICER1 mutations. Both families with multiple CN were found to have mutations in DICER1 leading to premature stop codons, predicted to result in loss of the ribonuclease and dsRNA binding domains. These domains are essential to the function of DICER1. No germline mutations were found in any of the 50 children who had developed WT. It has been established that DICER1 mutations cause familial CN and may be implicated in bilateral CN. No germline mutations were found in the patients with WT, suggesting that DICER1 mutations are unlikely to have a major role in the aetiology of sporadic WT. These results provide further evidence implicating miRNA dysregulation in tumourigenesis.
    Journal of Medical Genetics 10/2010; 47(12):863-6. DOI:10.1136/jmg.2010.081216 · 5.64 Impact Factor
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    ABSTRACT: JXG is a benign lesion of unknown incidence. It is the most frequent type of non-langerhans histiocytosis with a median age of 2 years. It usually presents as isolated cutaneous lesions. Multiple lesions, especially over the head and neck, may occur. The skin lesions tend to regress slowly with time. Extra-cutaneous and visceral involvements have been observed, the most common site being the eye. When the lesions are numerous, they may persist, hence the need for treatment with corticosteroids or chemotherapy. Histologically, the lesion consists of histiocytes admixed with an inflammatory infiltrate of variable density. The lesions are initially monomorphic and very cellular, progressively enriched with multinucleated giant cells of Touton and foamy cells, followed by spindle cells. We report an 8-year old girl with JXG of early type without multinucleated and foamy cells. This case presented as a tumour in the inferior meatus of nasal cavity, clinically simulating a rhabdomyosarcoma. This atypical clinical and histological presentation with benign evolution should be recognized since it requires only local treatment.
    Annales de Pathologie 10/2010; 30(5):374-7. DOI:10.1016/j.annpat.2010.07.013 · 0.29 Impact Factor
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    Julie Castilloux, Dorothée Bouron-Dal Soglio, Christophe Faure
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    ABSTRACT: Late complications of esophageal atresia (EA), particularly esophagitis and Barrett's esophagus, are increasingly being recognized. With the exception of patients with dysphagia associated with esophageal stricture, it is unknown whether patient symptomatology can predict endoscopic findings. Data regarding the digestive symptoms of patients who were referred to the EA multidisciplinary clinic from October 2005 to October 2008, and underwent upper gastrointestinal endoscopic evaluation, were systematically collected. Macroscopic and histological findings were analyzed. Endoscopy was considered normal if no esophagitis, intestinal metaplasia or gastric metaplasia (GM) was discerned. Sixty-three patients underwent endoscopy. Eighteen had dysphagia related to an esophageal stricture needing dilation and were subsequently excluded from the analysis. Forty-five patients (26 girls) with a median age of 7.3 years (range 0.4 to 17.9 years) were evaluated. Twenty-six patients (58%) were normal at endoscopy, 14 patients (31%) had esophagitis and 16 patients (36%) had GM. No intestinal metaplasia or adenocarcinoma was detected. Six patients with abnormal endoscopy results were asymptomatic. No correlation between digestive symptoms and endoscopy results was found. The present cross-sectional study showed that symptomatology was not predictive of abnormal endoscopy in EA patients. Esophagitis or GM may be discovered, even in the absence of symptoms, suggesting that physicians cannot rely solely on symptomatology to accurately evaluate the extent of these esophageal complications in this population.
    Canadian journal of gastroenterology = Journal canadien de gastroenterologie 05/2010; 24(5):312-6. · 1.97 Impact Factor
  • Ugur Halac, Rola Al Dhaybi, Julie Powell, Dorothée Bouron-Dal Soglio, Fernando Alvarez
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    ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.
    Journal of pediatric gastroenterology and nutrition 08/2009; 50(2):219-21. DOI:10.1097/MPG.0b013e31819a62f5 · 2.87 Impact Factor
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    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.
    Pediatric and Developmental Pathology 06/2009; 13(1):66-71. DOI:10.2350/09-02-0606-CR.1 · 0.86 Impact Factor
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    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.
    Human pathology 06/2009; 40(9):1347-52. DOI:10.1016/j.humpath.2009.01.021 · 2.81 Impact Factor
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    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.
    Pediatric and Developmental Pathology 03/2009; 12(5):390-3. DOI:10.2350/08-09-0531.1 · 0.86 Impact Factor
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    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.
    Pediatric and Developmental Pathology 03/2009; 12(5):371-3. DOI:10.2350/08-11-0553.1 · 0.86 Impact Factor

Publication Stats

272 Citations
112.81 Total Impact Points


  • 2006–2015
    • CHU Sainte-Justine
      • Department of Paediatric Surgery
      Montréal, Quebec, Canada
  • 2006–2014
    • Université de Montréal
      • Department of Pathology and Cell Biology
      Montréal, Quebec, Canada
  • 2010
    • McGill University
      • Department of Oncology
      Montréal, Quebec, Canada
  • 2008–2009
    • Government of Quebec
      Québec, Quebec, Canada