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1.
Pathologie (Heidelb) ; 43(Suppl 1): 50-55, 2022 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-36175666

RESUMO

Chordomas are rare malignant tumors of the axial skeleton with notochordal differentiation. From a morphological point of view, chordomas display a broad spectrum ranging from the classical, conventional form not otherwise specified (NOS) to forms with hepatoid or renal carcinoma-like differentiation or even poorly or dedifferentiated variants. The detection of brachyury is highly characteristic, though not exclusive. The morphological differential diagnosis from a benign notochordal tumor (BNCT) requires integration of imaging since BNCT is limited to the vertebral bodies and is not osteolytic. Targeted therapy is a current research focus and cell lines as in vitro models are a precondition for the establishment and validation of this approach.


Assuntos
Cordoma , Humanos , Cordoma/diagnóstico , Diagnóstico Diferencial , Diferenciação Celular
2.
HNO ; 69(3): 221-228, 2021 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-33095325

RESUMO

An 87-year-old patient reported a nodular, progressively enlarging mass of the anterior nasal septum leading to partial obstruction of the nostrils. The tumor showed no infiltration of the subcutis, bone, or paranasal sinuses in imaging or intraoperatively. Histological examination revealed a chondroid tumor with lobular growth and physaliferous cell morphology. Immunohistochemistry revealed a brachyury-positive tumor without EWSR1 rearrangement, leading to the diagnosis of a chondroid chordoma. The reported case demonstrates the differential diagnostic considerations pertaining to this rare tumor, which can also have an untypical and very rare extra-axial location. Review of the literature identified 34 primary extraosseous chordomas of the nose, nasopharynx, and paranasal sinuses, and allowed the nasal chordoma presented herein to be included in this group of extra-axial chordomas.


Assuntos
Cordoma , Seios Paranasais , Idoso de 80 Anos ou mais , Cordoma/diagnóstico por imagem , Cordoma/cirurgia , Humanos , Imuno-Histoquímica , Cavidade Nasal/diagnóstico por imagem , Cavidade Nasal/cirurgia , Septo Nasal/diagnóstico por imagem , Septo Nasal/cirurgia
3.
Pathologe ; 39(5): 451-456, 2018 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-30046846

RESUMO

This article presents the case of a metachronic multicentric giant cell tumor of bone (GCTB). The patient obtained his first diagnosis of GCTB in the left humerus at the age of 47 years. Furthermore, he suffered from a GCTB in the head of his 4th left metacarpal bone and from a recurrence of the latter. All tumors carried the characteristic H3F3A mutation, which was proven by Sanger sequencing and a mutation specific antibody. The case is the first description of a multicentric H3F3A mutated GCTB.


Assuntos
Neoplasias Ósseas , Tumor de Células Gigantes do Osso , Histonas/genética , Neoplasias Ósseas/genética , Tumor de Células Gigantes do Osso/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia
5.
Pathologe ; 39(2): 125-131, 2018 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-29110035

RESUMO

A giant cell tumor of bone (GCTB) is one of the giant cell-rich lesions of bone and has to be differentiated from non-ossifying fibroma, aneurysmatic bone cyst, chondroblastoma, "brown tumor" and osteosarcoma containing giant cells. A hallmark of GCTB is the presence of the distinct histone 3 (H3F3A) mutation G34W and its detection either by sequencing methods or using immunohistochemistry with a novel antibody against this mutational site. Worrisome is the fact that under denosumab therapy a histological change of the lesions can be seen and there are first reports of sarcomas arising after therapy. When diagnosing giant cell-rich lesions, pathologists should be aware of the various differential diagnoses and morphological spectrum within GCTB.


Assuntos
Neoplasias Ósseas , Tumor de Células Gigantes do Osso , Osteossarcoma , Histonas , Humanos , Imuno-Histoquímica
6.
Pathologe ; 39(2): 181-185, 2018 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-29018939

RESUMO

A 26-year-old woman presented with a painful bulge at the rima ani. The tumor was located in the presacral region. Histological examination revealed a well-circumscribed biphenotypical tumor with papillary configured myxoid areas and strongly sclerosing regions. This case of a myxopapillary ependymoma is a rare example of a myxoid neoplastic lesion in the sacral region.


Assuntos
Ependimoma , Adulto , Feminino , Humanos
7.
Pathologe ; 39(2): 117-124, 2018 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-29236139

RESUMO

Benign notochordal tumors (BNCT) and chordomas are primary bone tumors of the spine with a predominant localization in the sacrum and clival region followed by the vertebral bodies. Besides the most common variant (NOS [not otherwise specified] with hepatoid or renal carcinoma cell-like differentiation) chordomas with chondroid, and polymorphic to anaplastic morphology are described. An unfavorable variant are pediatric chordomas with a loss of INI-1. BNCT and chordomas are characterized by the following immunohistological profile: vimentin+, cytokeratin+/-, epithelial membrane antigen (EMA)+/-, S100 protein+/-, brachyury+. This profile helps to distinguish these tumors from other lesions such as chondrosarcoma, chordoid meningioma, and metastases of carcinoma.


Assuntos
Neoplasias Ósseas , Condrossarcoma , Cordoma , Criança , Humanos , Queratinas , Proteínas S100
8.
Int J Cancer ; 142(7): 1369-1378, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29148152

RESUMO

Chordoma is a rare bone tumor with a known intrinsic heterogeneity. Here, we address this tumor heterogeneity in a new cell culture model for tumor diversity and progression in chordoma. The three cell lines U-CH17P, U-CH17M, and U-CH17S were established from a primary sacral chordoma and its derived metastases, a soft tissue and a skin metastasis, respectively. The lesions had divergent differentiation patterns which are conserved in the derived cell lines making them a suitable in vitro model for the analysis of tumorigenesis in chordoma. A common feature of the three cell lines is the expression of typical chordoma markers, such as Brachyury, vimentin, cytokeratins, EMA and S100 protein. A comparison of the genomic aberrations by array comparative genomic hybridization of the cell lines and the corresponding parental tumor tissues revealed that the precursor cells of U-CH17P, U-CH17M and U-CH17S were already present in the primary tumor. Therefore, we show that clonal diversity of this chordoma exists in the primary tumor and that not all of these subclones tend to metastasize. All cell lines had a CDKN2A loss. A comparison of the gene expression profiles of the cell lines revealed significant differences in the expression of several genes like MAGEC2 and SEMA6A known to be associated with the tendency to metastasize or proliferation and migration. Since the underlying mechanisms of tumor progression in chordoma are still largely unclear, the three U-CH17 cell lines are a suitable in vitro model for elucidating chordoma oncobiology.


Assuntos
Neoplasias Ósseas , Técnicas de Cultura de Células/métodos , Linhagem Celular Tumoral/citologia , Cordoma , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Cordoma/genética , Cordoma/patologia , Progressão da Doença , Humanos
9.
Pathologe ; 36(4): 372-84, 2015 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-26175197

RESUMO

Chronic myeloid leukemia (CML) is diagnostically defined by the reciprocal translocation t(9;22)(q34;q11). This aberration can be detected by the BCR-ABL fluorescence in situ hybridization (FISH) technique. This article presents a comparative analysis of different commercially available FISH probes and different FISH protocols in order to optimize this technique on formalin-fixed and paraffin-embedded bone marrow trephine biopsies.


Assuntos
Medula Óssea/patologia , Proteínas de Fusão bcr-abl/análise , Proteínas de Fusão bcr-abl/genética , Hibridização in Situ Fluorescente/métodos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Biópsia por Agulha , Cromossomos Humanos Par 22 , Cromossomos Humanos Par 9 , Humanos , Hibridização in Situ Fluorescente/instrumentação , Sensibilidade e Especificidade , Translocação Genética
10.
Laryngorhinootologie ; 94(3): 189-95; quiz 196-8, 2015 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-25751774

RESUMO

Rheumatic disorders (rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, Wegener's granulomatosis, relapsing polychondritis) may affect the larynx. The clinical symptoms are often unspecific, leading to delayed diagnosis. Malignant tumours should be considered in differential diagnosis with necessitating biopsy. Treatment may require interdisciplinary approach together with a specialist in internal medicine and rheumatology.


Assuntos
Doenças da Laringe/diagnóstico , Doenças Reumáticas/diagnóstico , Comportamento Cooperativo , Diagnóstico Diferencial , Humanos , Comunicação Interdisciplinar , Doenças da Laringe/terapia , Doenças Reumáticas/terapia , Distúrbios da Voz/diagnóstico
11.
Mol Cell Probes ; 29(5): 291-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25771912

RESUMO

Identifying rare genetic forms of infantile cholestasis is challenging due to their similar clinical presentation and their diverse etiology. After exclusion of common non-genetic causes a huge list of rare differential diagnosis remains to be solved. More than 90 genes are associated with monogenic forms of infantile cholestasis, thus preventing routine genetic workup by Sanger sequencing. Here we demonstrate a next generation sequencing approach to discover the underlying cause in clinically well characterized patients in whom common causes of infantile cholestasis have been excluded. After validation of the analytical sensitivity massive parallel sequencing was performed for 93 genes in six prospectively studied patients. Six novel mutations (PKHD1: p.Thr777Met, p.Tyr2260Cys; ABCB11: p.Val1112Phe, c.611+1G > A, p.Gly628Trpfs*3 and NPC1: p.Glu391Lys) and two known pathogenic mutations were detected proving our multi gene panel for infantile cholestasis to be a sensitive and specific method overcoming the complexity of the phenotype-based, candidate gene approach. Three exemplary clinical cases of infants with cholestasis are presented and discussed in the context of their genetic and histopathological findings (autosomal recessive polycystic kidney disease, atypical PFIC and Niemann-Pick syndrome type C1). These case reports highlight the critical impact of integrating clinical, histopathological and genetic data during the process of multi gene panel testing to ultimately pinpoint rare genetic diagnoses.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Proteínas de Transporte/genética , Colestase/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Glicoproteínas de Membrana/genética , Receptores de Superfície Celular/genética , Análise de Sequência de DNA/métodos , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Colestase/genética , Predisposição Genética para Doença , Testes Genéticos/métodos , Humanos , Lactente , Peptídeos e Proteínas de Sinalização Intracelular , Mutação , Proteína C1 de Niemann-Pick , Fenótipo , Estudos Prospectivos , Doenças Raras/diagnóstico , Doenças Raras/genética , Sensibilidade e Especificidade
12.
Leukemia ; 29(7): 1564-70, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25687653

RESUMO

Prognostically relevant risk factors in patients with diffuse large B-cell lymphoma (DLBCL) have predominantly been evaluated in elderly populations. We tested whether previously described risk factors are also valid in younger, poor-prognosis DLBCL patients. Paraffin-embedded samples from 112 patients with de novo DLBCL, enrolled in the R-MegaCHOEP trial of the German High Grade Non-Hodgkin Lymphoma Study Group (DSHNHL) were investigated using immunohistochemistry (MYC, FOXP1, LMO2, GCET1, CD5, CD10, BCL2, BCL6, IRF4/MUM1) and fluorescence in situ hybridization (MYC, BCL2, BCL6). MYC, BCL2 and BCL6 breaks occurred in 14, 21 and 31%, respectively. In the majority of cases, MYC was simultaneously rearranged with BCL2 and/or BCL6. The adverse impact of MYC rearrangements was confirmed, but the sole presence of BCL2 breaks emerged as a novel prognostic marker associated with inferior overall survival (OS) (P=0.002). Combined overexpression of MYC and BCL2 showed only limited association with inferior OS. All immunohistochemical cell of origin classifiers applied failed to predict survival time. DLBCL tumors with significant proportion of immunoblastic and/or immunoblastic-plasmacytoid cells had inferior OS, independently from from BCL2 break. Younger, poor-prognosis DLBCL patients, therefore, display different biological risk factors compared with an elderly population, with BCL2 translocations emerging as a powerful negative prognostic marker.


Assuntos
Biomarcadores Tumorais/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Adolescente , Adulto , Biomarcadores Tumorais/genética , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-myc/genética , Fatores de Risco , Taxa de Sobrevida , Adulto Jovem
13.
Mol Cell Endocrinol ; 395(1-2): 41-50, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25102227

RESUMO

Brown and white adipocytes have been shown to derive from different progenitors. In this study we sought to clarify the molecular differences between human brown and white adipocyte progenitors cells. To this end, we performed comparative gene array analysis on progenitor cells isolated from paired biopsies of deep and subcutaneous neck adipose tissue from individuals (n = 6) undergoing neck surgery. Compared with subcutaneous neck progenitors, cells from the deep neck adipose tissue displayed marked differences in gene expression pattern, including 355 differentially regulated (>1.5 fold) genes. Analysis of highest regulated genes revealed that STMN2, MME, ODZ2, NRN1 and IL13RA2 genes were specifically expressed in white progenitor cells, whereas expression of LRRC17, CNTNAP3, CD34, RGS7BP and ADH1B marked brown progenitor cells. In conclusion, progenitors from deep neck and subcutaneous neck adipose tissue are characterized by a distinct molecular signature, giving rise to either brown or white adipocytes. The newly identified markers may provide potential pharmacological targets facilitating brown adipogenesis.


Assuntos
Adipócitos Marrons/metabolismo , Adipócitos Brancos/metabolismo , Adipogenia/fisiologia , Regulação da Expressão Gênica/fisiologia , Células-Tronco/metabolismo , Gordura Subcutânea/metabolismo , Adipócitos Marrons/citologia , Adipócitos Brancos/citologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pescoço , Análise de Sequência com Séries de Oligonucleotídeos , Especificidade de Órgãos , Células-Tronco/citologia , Gordura Subcutânea/citologia
15.
Z Gastroenterol ; 52(7): 657-62, 2014 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-25026008

RESUMO

INTRODUCTION: The coincidence of echinococcosis and hepatocellular carcinoma (HCC) is quite rare. We report the case of a 45-year-old man who was admitted to our hospital because of abdominal pain in the right upper quadrant and jaundice. Clinical features and diagnostics: There was no history of weight loss or fever. No abdominal mass was palpable. The laboratory reports showed increased transaminase levels. Ultrasonography revealed an inhomogenous, cystic lesion measuring 6 cm in diameter in the segments VI and VII. Serology for echinococcosis was negative, alpha-fetoprotein (AFP) was considerably increased. CT scan showed a solid mass of 3,7 cm in diameter adjacent to the cystic lesion. THERAPY AND COURSE: Anthelminthic therapy with albendazole caused a massive increase of cholestasis parameters and treatment had to be stopped. The simultaneous occurrence of serologically negative cystic echinococcosis and HCC was suspected and partial liver resection was performed. Histological examination confirmed both diagnoses and tumor resection in healthy tissue. 5 months after resection CT scan showed multicentric HCC affecting the whole liver. Palliative therapy with sorafenib was established. DISCUSSION: The coincidence of HCC and cystic echinococcosis in the non-cirrhotic liver of a young man is a rare event. Despite resection in healthy tissue multicentric HCC was diagnosed 5 months later. Only few cases of simultaneous occurrence of HCC and echinococcosis have been published so far. Some authors considered echinococcosis as a trigger for HCC. A causal link between both entities has not been demonstrated until now.


Assuntos
Cistos/patologia , Equinococose Hepática/patologia , Neoplasias Hepáticas/patologia , Lesões Pré-Cancerosas/patologia , Cistos/cirurgia , Diagnóstico Diferencial , Equinococose Hepática/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/cirurgia , Resultado do Tratamento
17.
Endocrinology ; 154(9): 3141-51, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23751871

RESUMO

Variants in the fat mass- and obesity-associated (FTO) gene are associated with obesity and body fat mass in genome-wide association studies. However, the mechanism by which FTO predisposes individuals to obesity is not clear so far. First mechanistic evidence was shown in Fto-negative mice. These mice are resistant to obesity due to enhanced energy expenditure, whereas the mass of brown adipose tissue remains unchanged. We hypothesize that FTO is involved in the induction of white adipose tissue browning, which leads to mitochondrial uncoupling and increases energy expenditure. Uncoupling protein 1 (Ucp-1) was significantly higher expressed in both gonadal and inguinal adipose depots of Fto(-/-) compared with Fto(+/+) littermates accompanied by the appearance of multivacuolar, Ucp-1-positive adipocytes in these tissues. By using lentiviral short hairpin RNA constructs, we established FTO-deficient human preadipocytes and adipocytes and analyzed key metabolic processes. FTO-deficient adipocytes showed an adipogenic differentiation rate comparable with control cells but exhibited a reduced de novo lipogenesis despite unchanged glucose uptake. In agreement with the mouse data, FTO-deficient adipocytes exhibited 4-fold higher expression of UCP-1 in mitochondria compared with control cells. The up-regulation of UCP-1 in FTO-deficient adipocytes resulted in enhanced mitochondrial uncoupling. We conclude that FTO deficiency leads to the induction of a brown adipocyte phenotype, thereby enhancing energy expenditure. Further understanding of the signaling pathway connecting FTO with UCP-1 expression might lead to new options for obesity and overweight treatment.


Assuntos
Tecido Adiposo Branco/metabolismo , Metabolismo Energético , Canais Iônicos/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas/metabolismo , Regulação para Cima , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/citologia , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Animais , Biomarcadores/metabolismo , Células Cultivadas , Feminino , Humanos , Gordura Intra-Abdominal/citologia , Gordura Intra-Abdominal/metabolismo , Canais Iônicos/biossíntese , Canais Iônicos/genética , Masculino , Camundongos , Camundongos Knockout , Proteínas Mitocondriais/biossíntese , Proteínas Mitocondriais/genética , Proteínas/antagonistas & inibidores , Proteínas/genética , Interferência de RNA , RNA Interferente Pequeno , Gordura Subcutânea/citologia , Gordura Subcutânea/metabolismo , Gordura Subcutânea Abdominal/citologia , Gordura Subcutânea Abdominal/metabolismo , Proteína Desacopladora 1 , Vacúolos/metabolismo
18.
Pathologe ; 34(3): 210-4, 2013 May.
Artigo em Alemão | MEDLINE | ID: mdl-23568339

RESUMO

Differentiation of chronic gastritis from marginal zone B-cell lymphoma (MZoL) of MALT type is often difficult for the pathologist. Diagnostic tools include CD20 stain to highlight lymphoepithelial lesions, Wotherspoon grading of the infiltrate, and clonality analysis of the B-cells. MZoL may partially transform into a diffuse, large B-cell lymphoma, which the authors have named blastic MZoL. Blastic MZoL may be present with or without small cell MZoL. Without this component, blastic MzoL, while being CD10-negative, is presently difficult to positively diagnose since specific immune markers are still lacking. Blastic MZoL has a very favourable outcome compared to conventional diffuse large B-cell lymphomas (DLBCL). Moreover, there are conventional DLBCL in the stomach, mostly in a setting of a secondary organ involvement. The biology of these gastric DLBCL is identical to their extragastric counterparts. This is also true for primary gastric Burkitt lymphoma and mucosal involvement in B-CLL or mantle cell lymphoma. Unfavourable outcomes are always observed for EBV-triggered lymphoproliferations in immunodeficiency and peripheral T-cell lymphomas which might also arise or be initially diagnosed in the stomach.


Assuntos
Comportamento Cooperativo , Comunicação Interdisciplinar , Linfoma de Zona Marginal Tipo Células B/patologia , Neoplasias Gástricas/patologia , Linfócitos B/patologia , Biomarcadores Tumorais/análise , Linfoma de Burkitt/patologia , Transformação Celular Neoplásica/patologia , Diagnóstico Diferencial , Mucosa Gástrica/patologia , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/patologia , Gradação de Tumores , Prognóstico
19.
Pathologe ; 34(4): 329-34, 2013 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-23179209

RESUMO

BACKGROUND: The detection of characteristic genomic aberrations by fluorescence in situ hybridization (FISH) has a high diagnostic impact on lymphomas according to the World Health Organization (WHO). To investigate the reproducibility of non-isotopic ISH results a multicenter trial was carried out involving eight institutes for hematopathology. MATERIAL AND METHODS: Analyses were performed on two diffuse large B-cell lymphomas (DLBCL) without known aberrations, on one follicular lymphoma with a IGH/BCL2 translocation and BCL6 split and on two B-cell lymphomas intermediate between DLBCL and Burkitt's lymphoma with c-MYC and BCL2 rearrangements, one with an additional BCL6 split. Break-apart probes for BCL6 and c-MYC, as well as fusion probes for the c-MYC/IGH and the IGH/BCL2 translocations were used. RESULTS: All aberrations were correctly detected by all centres and no false positive or false negative results were obtained. The numbers of positive cells varied from 25% to 94%. Pearson's correlation coefficient between the centres was always > 0.8. CONCLUSIONS: The ISH analysis of recurrent genomic aberrations in formalin-fixed paraffin-embedded (FFPE) tissue is a highly reproducible technique which yields substantial additive help for lymphoma diagnostics.


Assuntos
Aberrações Cromossômicas , Hibridização In Situ/métodos , Linfoma não Hodgkin/genética , Biomarcadores Tumorais/genética , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/genética , Linfoma de Burkitt/patologia , Proteínas de Ligação a DNA/genética , Diagnóstico Diferencial , Genes myc/genética , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Hibridização in Situ Fluorescente/métodos , Linfoma Folicular/diagnóstico , Linfoma Folicular/genética , Linfoma Folicular/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/patologia , Proteínas Proto-Oncogênicas c-bcl-6 , Garantia da Qualidade dos Cuidados de Saúde , Reprodutibilidade dos Testes , Translocação Genética/genética
20.
Mol Syndromol ; 3(3): 120-130, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23112754

RESUMO

Concurrent emergence of nephroblastoma (Wilms Tumor; WT) and neuroblastoma (NB) is rare and mostly observed in patients with severe subtypes of Fanconi anemia (FA) with or without VACTER-L association (VL). We investigated the hypothesis that early consequences of genomic instability result in shared regions with copy number variation in different precursor cells that originate distinct embryonal tumors. We observed a newborn girl with FA and VL (aplasia of the thumbs, cloacal atresia (urogenital sinus), tethered cord at L3/L4, muscular ventricular septum defect, and horseshoe-kidney with a single ureter) who simultaneously acquired an epithelial-type WT in the left portion of the kidney and a poorly differentiated adrenal NB in infancy. A novel homozygous germline frameshift mutation in PALB2 (c.1676_c1677delAAinsG) leading to protein truncation (pGln526ArgfsX1) inherited from consanguineous parents formed the genetic basis of FA-N. Spontaneous and induced chromosomal instability was detected in the majority of cells analyzed from peripheral lymphocytes, bone marrow, and cultured fibroblasts. Bone marrow cells also showed complex chromosome rearrangements consistent with the myelodysplastic syndrome at 11 months of age. Array-comparative genomic hybridization analyses of both WT and NB showed shared gains or amplifications within the chromosomal regions 11p15.5 and 17q21.31-q25.3, including genes that are reportedly implicated in tumor development such as IGF2, H19, WT2, BIRC5, and HRAS.

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