RESUMEN
Unicentric Castleman disease (UCD) is a rare lymphoproliferative disorder. Paraneoplastic pemphigus (PNP) is a major complication associated with poor UCD prognosis. However, the genomic profiles and prognostic biomarkers of PNP-associated UCD remain unclear. In this study, we performed whole-exome sequencing analysis for 28 matched tumor-normal pairs and 9 tumor-only samples to define the genomic landscape of Chinese patients with PNP-associated UCD. An integrative analysis was performed to identify somatic variants, the mutational signatures, and key pathways in tumors. Besides, we analyzed the relationship among mutated genes, clinical characteristics, and prognosis. Sixty-one somatic mutant genes were identified in >1 patient with PNP-associated UCD. Specifically, IL6ST and PDGFRB were the most frequently mutated genes (32%), followed by DPP6 (18%) and MUC4 (18%). Signaling molecules and interactions, cellular processes, and signal transduction pathways were enriched. Furthermore, we found that poor overall survival was related to IL6ST variants (P = .02). Finally, we classified PNP-associated UCD into 4 genomic subgroups: IL6ST, PDGFRB, IL6ST-PDGFRB, and an unknown subgroup. In summary, we defined the molecular profile of PNP-associated UCD and identified a potential molecular biomarker for predicting prognosis, which may provide therapeutic targets for treating this severe disorder.
Asunto(s)
Enfermedad de Castleman , Síndromes Paraneoplásicos , Pénfigo , Humanos , Enfermedad de Castleman/diagnóstico , Enfermedad de Castleman/genética , Enfermedad de Castleman/complicaciones , Pénfigo/genética , Pronóstico , Secuenciación del Exoma , Receptor beta de Factor de Crecimiento Derivado de Plaquetas , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/genética , Biomarcadores , Receptor gp130 de CitocinasRESUMEN
PURPOSE OF REVIEW: X-linked hypophosphatemia and tumor-induced osteomalacia are diseases characterized by hypophosphatemia with impaired proximal tubular phosphate reabsorption. Complete resection of responsible tumors is the first-line therapy for patients with tumor-induced osteomalacia. In contrast, phosphate and active vitamin D have been used for patients with X-linked hypophosphatemia and inoperable ones with tumor-induced osteomalacia. The purpose of this review is to summarize the pathogenesis of these diseases and discuss about the new treatment. RECENT FINDINGS: Excessive FGF23 production has been shown to underline several kinds of hypophosphatemic rickets/osteomalacia including X-linked hypophosphatemia and tumor-induced osteomalacia. Burosumab, an anti-FGF23 monoclonal antibody, was approved for clinical use, while the indications of burosumab are different depending on countries. The inhibition of excessive FGF23 activity has been approved as a new therapy for several kinds of hypophosphatemic diseases. Further studies are necessary to clarify the long-term effects and safety of burosumab.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Raquitismo Hipofosfatémico Familiar/tratamiento farmacológico , Raquitismo Hipofosfatémico Familiar/genética , Factor-23 de Crecimiento de Fibroblastos/genética , Osteomalacia/tratamiento farmacológico , Osteomalacia/genética , Síndromes Paraneoplásicos/tratamiento farmacológico , Síndromes Paraneoplásicos/genética , Animales , Enfermedades Genéticas Ligadas al Cromosoma X/tratamiento farmacológico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Humanos , RatonesRESUMEN
CONTEXT: Literature suggests that oncogenic osteomalacia is usually caused by a benign mesenchymal tumor secreting fibroblast growth factor subtype-23 (FGF-23), but the involvement of other phosphatonins has only been scarcely reported. We have previously published a seemingly typical case of oncogenic osteomalacia. Following curative neoplasm resection, we now report unique molecular characteristics and biology of this tumor. CASE DESCRIPTION: A 25-year-old man had been diagnosed with severe oncogenic osteomalacia that gradually crippled him over 6 years. 68Ga-DOTA-TATE positron emission tomography/computed tomography scan localized the culprit tumor to his left sole, which on resection revealed a deep fibrous histiocytoma displaying a proliferation of spindle cells with storiform pattern associated with multinucleated giant cells resembling osteoclasts. Circulating FGF-23, which was elevated more than 2-fold, declined to undetectable levels 24 h after surgery. Microarray analysis revealed increased tumor gene expression of the phosphatonins FGF-23, matrix extracellular phosphoglycoprotein (MEPE) and secreted frizzled-related protein subtype 4, with elevated levels of all 3 proteins confirmed through immunoblot analysis. Differential expression of genes involved in bone formation and bone mineralization were further identified. The patient made an astonishing recovery from being wheelchair bound to fully self-ambulant 2 months postoperatively. CONCLUSION: This report describes oncogenic osteomalacia due to a deep fibrous histiocytoma, which coincidentally has been found to induce profound muscle weakness via the overexpression of 3 phosphatonins, which resolved fully upon radical resection of the tumor. Additionally, genes involved in bone formation and bone remodeling contribute to the molecular signature of oncogenic osteomalacia.
Asunto(s)
Factores de Crecimiento de Fibroblastos/metabolismo , Histiocitoma Fibroso Benigno/metabolismo , Osteomalacia/etiología , Síndromes Paraneoplásicos/etiología , Neoplasias de los Tejidos Blandos/etiología , Adulto , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/genética , Enfermedades del Pie/diagnóstico , Enfermedades del Pie/etiología , Enfermedades del Pie/genética , Enfermedades del Pie/metabolismo , Regulación Neoplásica de la Expresión Génica , Histiocitoma Fibroso Benigno/complicaciones , Histiocitoma Fibroso Benigno/diagnóstico , Histiocitoma Fibroso Benigno/genética , Humanos , Malasia , Masculino , Osteomalacia/diagnóstico , Osteomalacia/genética , Osteomalacia/metabolismo , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/genética , Síndromes Paraneoplásicos/metabolismo , Singapur , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/metabolismoRESUMEN
Tumour-induced osteomalacia (TIO) is a very rare paraneoplastic syndrome with bone pain, fractures and muscle weakness, which is mostly caused by phosphaturic mesenchymal tumours (PMTs). Cell-free DNA (cfDNA) has been regarded as a non-invasive liquid biopsy for many malignant tumours. However, it has not been studied in benign tumours, which prompted us to adopt the targeted next-generation sequencing approach to compare cfDNAs of 4 TIO patients, four patients with bone metastasis (BM) and 10 healthy controls. The mutational landscapes of cfDNA in TIO and BM groups were similar in the spectrum of allele frequencies and mutation types. Markedly, deleterious missense mutations in FGFR1 and loss-of-function mutations in MED12 were found in 3/4 TIO patients but none of BM patients. The gene ontology analysis strongly supported that these mutated genes found in TIOs would play a potential role in PMTs' process. The genetic signatures and corresponding change in expression of FGFR1 and FGF23 were further validated in PMT tissues from a test cohort of another three TIO patients. In summary, we reported the first study of the mutational landscape and genetic signatures of cfDNA in TIO/PMTs.
Asunto(s)
Ácidos Nucleicos Libres de Células , Análisis Mutacional de ADN , Neoplasias/complicaciones , Neoplasias/genética , Osteomalacia/complicaciones , Osteomalacia/genética , Síndromes Paraneoplásicos/complicaciones , Síndromes Paraneoplásicos/genética , Adulto , Biomarcadores de Tumor , Neoplasias Óseas/complicaciones , Neoplasias Óseas/genética , Estudios de Casos y Controles , Sistema Libre de Células , Femenino , Factor-23 de Crecimiento de Fibroblastos , Perfilación de la Expresión Génica , Biblioteca de Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Hipofosfatemia Familiar/metabolismo , Masculino , Complejo Mediador/genética , Persona de Mediana Edad , Mutación , Mutación Missense , Metástasis de la Neoplasia , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genéticaRESUMEN
Paraneoplastic autoimmune multiorgan syndrome (PAMS) is characterized by a heterogenous group of signs and symptoms including severe desquamative stomatitis, a polymorphous cutaneous eruption, humoral immunity against plakin proteins, contribution of cell-mediated autoimmunity and commonly a progressive respiratory failure. Autoantibodies in PAMS target a wide array of antigens including plakins, cadherins, alpha-2-macroglobulin like 1 (A2ML1), BP180, plakophilin-3, and several neuromuscular antigens. Originally described as paraneoplastic pemphigus in 1990 due to some of its clinical and immunologic similarities to classic pemphigus (pemphigus vulgaris and pemphigus foliaceus), PAMS is a multiorganopathy with several distinct features from these classic forms of pemphigus. Epidemiologically, PAMS is associated with underlying neoplasia and has a differing HLA-II allele predisposition compared to classic forms of pemphigus. Clinically, lesion morphology is polymorphous, and lesion distribution fundamentally differs from that seen in classic pemphigus. PAMS has a significantly higher mortality rate and a poorer response to treatments typically effective in pemphigus. Histologically, PAMS is characterized by the presence of interface dermatitis, vacuolar changes, and dyskeratotic keratinocytes which are not seen in classic pemphigus. PAMS demonstrates not only intercellular IgG as seen in classic pemphigus, but the presence of linear basement membrane zone deposition. Antibodies against desmoglein 3 (Dsg3) map to a broader array of epitopes than in pemphigus vulgaris and there is a higher prevalence of complement binding anti-Dsg3 IgG autoantibodies in PAMS. Autoantibodies can in rare cases be absent in the more cell-mediated form of PAMS. Considering these numerable differences, we review the entity of PAMS, and provide similarities and differences to classic forms of pemphigus.
Asunto(s)
Síndromes Paraneoplásicos/fisiopatología , Autoanticuerpos/inmunología , Autoantígenos/inmunología , Humanos , Neoplasias/complicaciones , Síndromes Paraneoplásicos/complicaciones , Síndromes Paraneoplásicos/tratamiento farmacológico , Síndromes Paraneoplásicos/genética , Pénfigo/complicacionesRESUMEN
Paraneoplastic neurological syndromes are very rare and often associated to breast, ovarian and small cells lung cancers. Paraneoplastic motor neuron diseases (MNDs) are even rarer, and frequently described in patients with breast cancer. We presented the first case of patient affected by HER2-positive breast tumor and possible paraneoplastic lower motor neuron disease. In literature, few cases are reported but no one highlights the tumor receptors' profile. Instead, HER2-positive breast cancers are prone to be related to anti-Yo-associated paraneoplastic cerebellar disorders. Anti-onconeural antibodies positivity can be rarely found, confirming that paraneoplastic MND have no specific biomarkers. The presence of CSF oligoclonal bands (OBs) suggests the presence of immune-mediated mechanism, in absence of other possible OBs causes.
Asunto(s)
Neoplasias de la Mama/líquido cefalorraquídeo , Enfermedad de la Neurona Motora/líquido cefalorraquídeo , Metástasis de la Neoplasia/patología , Bandas Oligoclonales/líquido cefalorraquídeo , Síndromes Paraneoplásicos/líquido cefalorraquídeo , Receptor ErbB-2/genética , Autoanticuerpos/líquido cefalorraquídeo , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/genética , Humanos , Enfermedad de la Neurona Motora/diagnóstico , Enfermedad de la Neurona Motora/genética , Neuronas Motoras , Proteínas del Tejido Nervioso/genética , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/genéticaRESUMEN
Context: Hyperglucagonemia in the absence of glucagonomas is rare. Biallelic-inactivating mutations in the glucagon receptor gene (GCGR) cause glucagon cell hyperplasia and neoplasia (GCHN), also termed Mahvash syndrome. Here, we report the first case to our knowledge of GCHN presenting with hypercalcemia and demonstrate a unique relationship between calcium and α-cell hyperplasia. Case Description: A 47-year-old man presented with severe PTH-independent hypercalcemia, 13.95 mg/dL (3.48 mmol/L). Imaging and extensive pathology tests yielded no conclusive cause. Glucagon levels >300 times the upper limit of normal were discovered. Subtotal pancreatectomy identified α-cell hyperplasia and neoplasia with metastatic disease in lymph nodes. Genomic analysis confirmed a homozygous missense variant in GCGR (Asp63Asn). This is a previously described pathologic variant and has a known association with GCHN. Conclusions: Inactivating mutations of the glucagon receptor gene lead to nonfunctional hyperglucagonemia and are associated with GCHN. Homozygous or compound heterozygous GCGR mutations are associated with α-cell hyperplasia, a known precursor to pancreatic neuroendocrine tumors that can metastasize. Hypercalcemia is an unreported consequence of GCHN with an unclear mechanism.
Asunto(s)
Carcinoma Neuroendocrino/genética , Células Secretoras de Glucagón/patología , Hipercalcemia/genética , Neoplasias Pancreáticas/genética , Carcinoma Neuroendocrino/complicaciones , Carcinoma Neuroendocrino/secundario , Glucagón/sangre , Humanos , Hipercalcemia/etiología , Hiperplasia/genética , Metástasis Linfática , Masculino , Persona de Mediana Edad , Mutación Missense , Neoplasias Pancreáticas/complicaciones , Síndromes Paraneoplásicos/etiología , Síndromes Paraneoplásicos/genética , Receptores de Glucagón/genética , SíndromeRESUMEN
Renal cell carcinoma is historically known as the 'great masquerader' with 40% of patients experiencing a paraneoplastic syndrome. Translocation carcinoma represents one-third of renal cancer in paediatric patients but less than 3% of renal cancers in patients aged 18-45 years where the clinical course is often rapidly terminal. There are less than 10 reported cases of leucoclastic vasculitis associated with clear cell carcinoma reported in the literature and 10 case reports of translocation carcinoma in adults. To our knowledge, we present the first reported case of Xp11 translocation carcinoma presenting as cutaneous vasculitis, as part of a paraneoplastic syndrome, in an adult patient. Our case highlights that renal cell cancers are truly the 'great masquerader' and a rash can be the first sign of renal malignancy.
Asunto(s)
Carcinoma de Células Renales/genética , Neoplasias Renales/genética , Síndromes Paraneoplásicos/genética , Vasculitis Leucocitoclástica Cutánea/etiología , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/terapia , Quimioradioterapia Adyuvante/métodos , Diagnóstico Diferencial , Humanos , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Síndromes Paraneoplásicos/patología , Tomografía Computarizada por Rayos X/métodos , Translocación Genética , Resultado del Tratamiento , Vasculitis Leucocitoclástica Cutánea/patología , Vena Cava Inferior/diagnóstico por imagen , Vena Cava Inferior/patologíaRESUMEN
Systemic sclerosis (SSc) is an autoimmune connective tissue disorder, characterized by multisystem involvement, vasculopathy, and fibrosis. An increased risk of malignancy is observed in SSc (including breast and lung cancers), and in a subgroup of patients with specific autoantibodies (i.e., anti-RNA polymerase III and related autoantibodies), SSc could be a paraneoplastic syndrome and might be directly related to an immune response against cancer. Herein, we reviewed the literature, focusing on the most recent articles, and shed light onto the potential relationship between cancer and scleroderma regarding temporal and immunological dimensions.
Asunto(s)
Autoanticuerpos/inmunología , Enfermedades Autoinmunes/inmunología , Neoplasias/inmunología , Síndromes Paraneoplásicos/inmunología , Esclerodermia Sistémica/inmunología , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/patología , Fibrosis , Humanos , Neoplasias/complicaciones , Neoplasias/genética , Síndromes Paraneoplásicos/complicaciones , Síndromes Paraneoplásicos/genética , ARN Polimerasa III/inmunología , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/genética , Esclerodermia Sistémica/patología , Piel/inmunología , Piel/patologíaAsunto(s)
Leucemia Linfocítica Granular Grande/diagnóstico , Síndromes Paraneoplásicos/diagnóstico , Biopsia , Diagnóstico Diferencial , Humanos , Inmunofenotipificación , Úlcera de la Pierna/diagnóstico , Úlcera de la Pierna/genética , Úlcera de la Pierna/patología , Leucemia Linfocítica Granular Grande/genética , Leucemia Linfocítica Granular Grande/patología , Masculino , Síndromes Paraneoplásicos/genética , Piel/patologíaRESUMEN
Dermatomyositis (DM) is a type of autoimmune inflammatory myopathy, which primarily affects the skin and muscle. The underlying mechanisms of DM remain poorly understood. The present study aimed to explore gene expression profile alterations, investigate the underlying mechanisms, and identify novel targets for DM. The GSE48280 dataset, which includes data from five DM and five normal muscle tissue samples, was obtained from the Gene Expression Omnibus. Firstly, differentially expressed genes (DEGs) were screened by limma package in R. Subsequently, functional and pathway enrichment analyses were performed using ClueGO from Cytoscape. Finally, proteinprotein interaction (PPI) networks were constructed using STRING and Cytoscape, in order to identify hub genes. As a result, 180 upregulated and 21 downregulated genes were identified in the DM samples. The Gene Ontology enrichment analysis revealed that the type I interferon (IFN) signaling pathway was the most significantly enriched term within the DEGs. The Kyoto Encyclopedia of Genes and Genomes pathway analysis identified 27 significant pathways, the majority of which can be divided into the infectious diseases and immune system categories. Following construction of PPI networks, 24 hub genes were selected, all of which were associated with the type I IFN signaling pathway in DM. The findings of the present study indicated that type I IFNs may have a central role in the induction of DM. In addition, other DEGs, including chemokine (CC motif) ligand 5, CXC motif chemokine 10, Tolllike receptor 3, DEXD/HBox helicase 58, interferon induced with helicase C domain 1, interferonstimulated gene 15 and MX dynaminlike GTPase 1, may be potential targets for DM diagnosis and treatment.
Asunto(s)
Dermatomiositis/genética , Síndromes Paraneoplásicos/genética , Transcriptoma , Biología Computacional , Dermatomiositis/metabolismo , Perfilación de la Expresión Génica , Ontología de Genes , Redes Reguladoras de Genes , Humanos , Síndromes Paraneoplásicos/metabolismo , Mapas de Interacción de ProteínasRESUMEN
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a highly aggressive neoplasm that typically occurs in young females. Paraneoplastic hypercalcemia is associated in two thirds of the cases. Recent studies demonstrated that this rare tumor harbors the same molecular features of malignant rhabdoid tumor secondary to SMARCA4/BRG1 mutations. We illustrate herein a typical bilateral case of SCCOHT with comprehensive molecular characterization in a 14-year-old girl. We also discuss the value of SMARCA4 immunostaining in the diagnostic approach of undifferentiated ovarian and pelvic malignancies.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma de Células Pequeñas/genética , ADN Helicasas/genética , Mutación de Línea Germinal , Hipercalcemia/genética , Proteínas Nucleares/genética , Neoplasias Ováricas/genética , Síndromes Paraneoplásicos/genética , Factores de Transcripción/genética , Adolescente , Biomarcadores de Tumor/análisis , Biopsia , Neoplasias Óseas/genética , Neoplasias Óseas/secundario , Carcinoma de Células Pequeñas/química , Carcinoma de Células Pequeñas/secundario , Carcinoma de Células Pequeñas/cirugía , Quimioterapia Adyuvante , ADN Helicasas/análisis , Análisis Mutacional de ADN , Progresión de la Enfermedad , Resultado Fatal , Femenino , Predisposición Genética a la Enfermedad , Humanos , Hipercalcemia/patología , Inmunohistoquímica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundario , Imagen por Resonancia Magnética , Proteínas Nucleares/análisis , Neoplasias Ováricas/química , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Síndromes Paraneoplásicos/patología , Fenotipo , Valor Predictivo de las Pruebas , Factores de Tiempo , Tomografía Computarizada por Rayos X , Factores de Transcripción/análisis , Resultado del TratamientoRESUMEN
Idiopathic inflammatory myopathies (IIMs) are autoimmune diseases with an underlying yet undefined genetic component. Recently, phospholipase C-like 1 (PLCL1) has been identified as a potential genetic susceptibility locus for dermatomyositis (DM) in patients of European ancestry. Here, association between PLCL1 polymorphisms and IIMs was investigated in Chinese Han. Genomic DNA was isolated from blood samples (2 mL) collected from Chinese Han (≥18 years) with polymyositis (PM, n = 286) or dermatomyositis (DM, n = 535) and ethnically matched controls (n = 968). Patients and controls were genotyped for five SNPs (rs938929, rs1518364, rs6738825, rs2117339, and rs7572733) previously associated with DM, with the Sequenom MassARRAY system. SNPs rs6738825 and rs7572733 were found to be associated with the development of DM in Chinese Han (P c = 0.015; P c = 0.025, respectively) as well as the risk A allele of rs938929 and T allele of rs1518364 (P c = 0.030; P c = 0.029). None of the five SNPs were associated with PM (all P c > 0.05). The frequency of the two haplotypes of these five SNPs was also significantly different between DM patients and healthy controls. In addition, conditional analysis with rs6738825 revealed that these SNPs were not independent factors contributing to DM. Finally, a novel association between rs6738825 and rs7572733 and DM with complicating interstitial lung disease was observed (ILD; P c = 0.040; P c = 0.030, respectively). A positive association between PLCL1 polymorphisms and DM patients and DM patients with ILD was observed, indicating that PLCL1 might be the susceptibility gene for DM patients in Chinese Han.
Asunto(s)
Dermatomiositis/genética , Miositis/genética , Síndromes Paraneoplásicos/genética , Fosfoinositido Fosfolipasa C/genética , Adulto , China , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
INTRODUCTION: Whether motor neuron diseases (MNDs) can be considered in some cases of paraneoplastic syndromes is controversial. We report a case of rapidly progressive motor neuronopathy following a diagnosis of breast carcinoma, with a presence of anti-Ri antibodies, and a novel SOD1 gene mutation. OBSERVATION: An 80-year-old woman with mucinous adenocarcinoma of the left breast for 4 years developed sub-acute quadriparesis. Myography revealed chronic denervation signs. The patient had serum anti-Ri onconeural antibodies. The diagnosis of paraneoplastic MND was established. Because of a familial history of ALS, a genetic analysis for familial ALS was performed. We identified a novel heterozygous mutation in SOD1 gene, SOD I18del. This mutation may reflect a genetic predisposition to develop a MND, inducing fragility of motor neurons. Neurological improvement was observed after three months of both intravenous gamma globulin and corticosteroids. CONCLUSION: The present observation supports the idea that MND can be considered as a paraneoplastic syndrome. A combination of anti-Ri onconeural antibodies and a particular SOD1 gene mutation, consisting in risk factor, might be in cause in the process of motor neuron death. When in doubt, paraneoplastic cause should be suspected in the differential diagnosis of MND. Immunotherapy treatment may lead to a favorable outcome.
Asunto(s)
Antígenos de Neoplasias/inmunología , Enfermedad de la Neurona Motora/genética , Proteínas del Tejido Nervioso/inmunología , Síndromes Paraneoplásicos/genética , Proteínas de Unión al ARN/inmunología , Eliminación de Secuencia/genética , Superóxido Dismutasa/genética , Anciano de 80 o más Años , Animales , Anticuerpos/sangre , Femenino , Humanos , Modelos Moleculares , Enfermedad de la Neurona Motora/complicaciones , Antígeno Ventral Neuro-Oncológico , Síndromes Paraneoplásicos/complicaciones , Superóxido Dismutasa-1RESUMEN
Pancreatic cancer (PC) has a high rate of mortality and a poorly understood mechanism of progression. Investigation of the molecular mechanism of PC and exploration of the specific markers for early diagnosis and specific targets of therapy are key points to prevent and treat PC effectively and to improve their prognosis. In our study, expression profiles experiment of para-carcinoma, carcinoma and relapse human PC was performed using Agilent human whole genomic oligonucleotide microarrays with 45 000 probes. Differentially expressed genes related with PC were screened and analysed further by Gene Ontology term analysis and Kyoto encyclopaedia of genes and genomes pathway analysis. Our results showed that there were 3853 differentially expressed genes associated with pancreatic carcinogenesis and relapse. In addition, our study found that PC was related to the Jak-STAT signalling pathway, PPAR signalling pathway and Calcium signalling pathway, indicating their potential roles in pancreatic carcinogenesis and progress.
Asunto(s)
Neoplasias Pancreáticas/metabolismo , Síndromes Paraneoplásicos/metabolismo , Carcinogénesis/genética , Carcinogénesis/metabolismo , Perfilación de la Expresión Génica , Ontología de Genes , Humanos , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/prevención & control , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias Pancreáticas/genética , Síndromes Paraneoplásicos/genética , Transducción de Señal , Neoplasias PancreáticasAsunto(s)
Síndrome de Birt-Hogg-Dubé/patología , Síndromes Paraneoplásicos/patología , Proteínas Proto-Oncogénicas/genética , Enfermedades Cutáneas Papuloescamosas/patología , Proteínas Supresoras de Tumor/genética , Biopsia con Aguja , Síndrome de Birt-Hogg-Dubé/diagnóstico , Síndrome de Birt-Hogg-Dubé/genética , Diagnóstico Diferencial , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Nariz , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/genética , Enfermedades Cutáneas Papuloescamosas/diagnóstico , Rondas de EnseñanzaRESUMEN
Chronic basophilic leukemia (CBL) is an extremely rare disorder. A female patient presented with recurrent attacks of chills, fever and abdominal pain was found to have simultaneous cyclic oscillation in leukocyte counts and C-reactive protein values. She was initially diagnosed with familial Mediterranean fever and treated with colchicine. Diagnosis of CBL was established by morphologic studies of peripheral blood and bone marrow. Her febrile attacks recurred with marked elevation in serum interleukin-6 (IL-6) level when basophil counts climbed to peak levels during cyclic oscillation. Molecular studies by real-time PCR showed IL-6 gene expression in neoplastic basophils separated by magnetic-activated cell sorting infiltrating the bone marrow, suggesting that IL-6 is released by neoplastic basophils of an underlying CBL, resulting in a new paraneoplastic syndrome that mimics autoinflammatory disorders.
Asunto(s)
Basófilos/patología , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Síndromes Paraneoplásicos/etiología , Anciano , Basófilos/metabolismo , Análisis Químico de la Sangre , Médula Ósea/patología , Aberraciones Cromosómicas , Femenino , Expresión Génica , Humanos , Inmunofenotipificación , Interleucina-6/sangre , Interleucina-6/genética , Janus Quinasa 2/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Mutación , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/genéticaRESUMEN
Cutaneous findings are not uncommonly a concomitant finding in patients afflicted with gastrointestinal (GI) diseases. The dermatologic manifestations may precede clinically evident GI disease. Part I of this 2-part CME review focuses on dermatologic findings as they relate to hereditary and nonhereditary polyposis disorders and paraneoplastic disorders. A number of hereditary GI disorders have an increased risk of colorectal carcinomas. These disorders include familial adenomatous polyposis, Peutz-Jeghers syndrome, and juvenile polyposis syndrome. Each disease has its own cutaneous signature that aids dermatologists in the early diagnosis and detection of hereditary GI malignancy. These disease processes are associated with particular gene mutations that can be used in screening and to guide additional genetic counseling. In addition, there is a group of hamartomatous syndromes, some of which are associated with phosphatase and tensin homolog (PTEN) gene mutations, which present with concurrent skin findings. These include Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, and Cronkhite-Canada syndrome. Finally, paraneoplastic disorders are another subcategory of GI diseases associated with cutaneous manifestations, including malignant acanthosis nigricans, Leser-Trélat sign, tylosis, Plummer-Vinson syndrome, necrolytic migratory erythema, perianal extramammary Paget disease, carcinoid syndrome, paraneoplastic dermatomyositis, and paraneoplastic pemphigus. Each of these disease processes have been shown to be associated with an increased risk of GI malignancy. This underscores the important role of dermatologists in the diagnosis, detection, monitoring, and treatment of these disorders while consulting and interacting with their GI colleagues.
Asunto(s)
Enfermedades Gastrointestinales/complicaciones , Neoplasias Gastrointestinales/complicaciones , Enfermedades Cutáneas Genéticas/etiología , Acantosis Nigricans/genética , Poliposis Adenomatosa del Colon/genética , Carcinoma Basocelular/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/etiología , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Dermatomiositis/genética , Enfermedades Gastrointestinales/genética , Neoplasias Gastrointestinales/patología , Síndrome de Hamartoma Múltiple/diagnóstico , Síndrome de Hamartoma Múltiple/genética , Histiocitoma Fibroso Benigno/genética , Humanos , Hipotricosis/genética , Poliposis Intestinal/genética , Síndrome Carcinoide Maligno/genética , Mutación , Eritema Necrolítico Migratorio/diagnóstico , Eritema Necrolítico Migratorio/genética , Fosfohidrolasa PTEN/genética , Síndromes Paraneoplásicos/complicaciones , Síndromes Paraneoplásicos/genética , Síndrome de Peutz-Jeghers/genética , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/secundarioRESUMEN
Although they may sometimes appear similar, paraneoplastic autoimmunity has a unique pathogenesis, different from the classical autoimmune diseases not associated with cancer. When distinguished clinically, paraneoplastic autoimmunity is more severe and often presents with a broader range of clinical signs and symptoms. Management of these patients is difficult and is usually centered in part on treatment of the underlying malignancy. Self-antigens recognized in the setting of paraneoplastic autoimmunity can be diverse, and the number of determinants recognized within a single antigen can be numerous. This review uses prototypic examples of paraneoplastic immune-mediated diseases and their associated malignancies to describe the mechanisms by which immune dysregulation can occur in the setting of cancer. Specific diseases covered include paraneoplastic pemphigus, Sweet's syndrome, pyoderma gangrenosum, thymoma-associated multiorgan autoimmunity, myasthenia gravis, autoimmune hemolytic anemia, immune thrombocytopenia, and the paraneoplastic neurological syndromes. The malignancies discussed include thymoma, non-Hodgkin's lymphoma, and chronic lymphocytic leukemia, among others. The mechanisms by which cancers induce autoimmunity are broken down into the following categories: disruption of central tolerance, peripheral immune dysregulation, and alteration of self-antigens. For each category, examples of paraneoplastic autoimmune diseases and their associated malignancies are discussed. Finally, mechanisms by which cancer treatment can lead to autoimmunity and examples of polymorphisms that are linked to both cancer and autoimmunity are discussed.
Asunto(s)
Autoantígenos/inmunología , Enfermedades Autoinmunes/inmunología , Transformación Celular Neoplásica/inmunología , Síndromes Paraneoplásicos/inmunología , Piel/patología , Animales , Enfermedades Autoinmunes/genética , Predisposición Genética a la Enfermedad , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/inmunología , Humanos , Tolerancia Inmunológica/genética , Tolerancia Inmunológica/inmunología , Síndromes Paraneoplásicos/genética , Polimorfismo Genético , Piel/inmunologíaRESUMEN
Multicentric reticulohistiocytosis (MR) is a rare non-Langerhans histiocytosis that is characterized by cutaneous nodules and severe destructive arthritis. Although 25-30% of reported cases have been associated with internal malignancies, the pathophysiology of MR is unknown. Herein, we report two cases of MR that were associated with urologic neoplasms. Because the tumor suppressor gene p53 may play a role in the biology of other histiocytoses, we investigated its p53 immunoexpression in these two cases. Both cases were positive immunohistochemically, but it remains to be seen whether this finding is truly important in the pathogenesis of MR associated with underlying visceral neoplasms.