RESUMEN
BACKGROUND: Mastocytosis is characterised by the presence of abnormal quantities of mastocytes in one or more organs. Although it occurs in systemic forms of mastocytosis, isolated skin involvement is the predominant presentation, particularly in children, in the form of more or less extensive though non-systematic lesions. Herein, we report a case of maculopapular cutaneous mastocytosis that is unusual in terms of its metameric topography. PATIENTS AND METHODS: A 16-year-old youth presented with an erythematous maculopapular rash of 18 months' duration and involving pruritic inflammatory episodes strictly localised in segment T8 to the left. The skin biopsy showed a significant increase in the number of dermal mastocytes (CD117+). No KIT mutations were found in the skin lesions nor in the unimpaired skin of the opposite side. Further investigations ruled out systemic mastocytis. DISCUSSION: Herein, we report a case of cutaneous mastocytosis that is unusual in terms of its metameric disposition. There have been only two previous reports of segmental cutaneous mastocytis. The two pathological hypotheses involved precessional dermatitis that renders the skin surface susceptible to homing, and somatic mosaicism (type 1) with local mastocyte proliferation.
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Mastocitos/patología , Mastocitosis Cutánea/patología , Adolescente , Biopsia , Diagnóstico Diferencial , Humanos , Masculino , Piel/patologíaRESUMEN
Dihydropyrimidine dehydrogenase is a crucial enzyme for the degradation of 5-fluorouracil (5FU). DPYD, which encodes dihydropyrimidine dehydrogenase, is prone to acquire genomic rearrangements because of the presence of an intragenic fragile site FRA1E. We evaluated DPYD copy number variations (CNVs) in a prospective series of 242 stage I-III colorectal tumours (including 87 patients receiving 5FU-based treatment). CNVs in one or more exons of DPYD were detected in 27% of tumours (deletions or amplifications of one or more DPYD exons observed in 17% and 10% of cases, respectively). A significant relationship was observed between the DPYD intragenic rearrangement status and dihydropyrimidine dehydrogenase (DPD) mRNA levels (both at the tumour level). The presence of somatic DPYD aberrations was not associated with known prognostic or predictive biomarkers, except for LOH of chromosome 8p. No association was observed between DPYD aberrations and patient survival, suggesting that assessment of somatic DPYD intragenic rearrangement status is not a powerful biomarker to predict the outcome of 5FU-based chemotherapy in patients with colorectal cancer.
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Neoplasias Colorrectales/genética , Dihidrouracilo Deshidrogenasa (NADP)/genética , Reordenamiento Génico/genética , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Variaciones en el Número de Copia de ADN/genética , Exones/genética , Femenino , Fluorouracilo/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , ARN Mensajero/genéticaRESUMEN
BACKGROUND: To test the prognostic value of tumour protein and genetic markers in colorectal cancer (CRC) and examine whether deficient mismatch repair (dMMR) tumours had a distinct profile relative to proficient mismatch repair (pMMR) tumours. METHODS: This prospective multicentric study involved 251 stage I-III CRC patients. Analysed biomarkers were EGFR (binding assay), VEGFA, thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) expressions, MMR status, mutations of KRAS (codons 12-13), BRAF (V600E), PIK3CA (exons 9 and 20), APC (exon 15) and P53 (exons 4-9), CpG island methylation phenotype status, ploidy, S-phase, LOH. RESULTS: The only significant predictor of relapse-free survival (RFS) was tumour staging. Analyses restricted to stage III showed a trend towards a shorter RFS in KRAS-mutated (P=0.005), BRAF wt (P=0.009) and pMMR tumours (P=0.036). Deficient mismatch repair tumours significantly demonstrated higher TS (median 3.1 vs 1.4) and TP (median 5.8 vs 3.5) expression relative to pMMR (P<0.001) and show higher DPD expression (median 14.9 vs 7.9, P=0.027) and EGFR content (median 69 vs 38, P=0.037) relative to pMMR. CONCLUSIONS: Present data suggesting that both TS and DPD are overexpressed in dMMR tumours as compared with pMMR tumours provide a strong rationale that may explain the resistance of dMMR tumours to 5FU-based therapy.
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Adenocarcinoma/genética , Neoplasias Colorrectales/genética , Dihidrouracilo Deshidrogenasa (NADP)/metabolismo , Recurrencia Local de Neoplasia/genética , Timidilato Sintasa/metabolismo , Adenocarcinoma/enzimología , Adenocarcinoma/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/farmacología , Antimetabolitos Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/mortalidad , Reparación de la Incompatibilidad de ADN , Análisis Mutacional de ADN , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Femenino , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Francia , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Polimorfismo Genético , Modelos de Riesgos Proporcionales , Estudios ProspectivosRESUMEN
Based on nationwide data from the French national cancer institute (INCa), we analyzed the evolution of cancer genetics consultations and testing over time, and the uptake of targeted tests in relatives of families with BRCA1/2 or MMR genes mutation. Genetic testing and consultations for familial high-risk individuals are exclusively funded and monitored by the INCa in France. All nationwide cancer genetics centers reported annually standardized parameters of activity from 2003 to 2011. The analysis included a total of 240,134 consultations and 134,652 genetic tests enabling to identify 32,494 mutation carriers. Referral for hereditary breast and ovarian cancer (HBOC) or colorectal cancer predisposition syndromes represented 59 % (141,639) and 23.2 % (55,698) consultations, respectively. From 2003 to 2011, we found a dramatic and steady increase of tests performed for BRCA1/2 (from 2,095 to 7,393 tests/year, P < 0.0001) but not for MMR genes (from 1,144 to 1,635/year, P = NS). The overall percentage of deleterious mutations identified in the probands tested was 13.8 and 20.9 % in HBOC and Lynch syndromes, respectively. Pooled analysis for BRCA1/2 and Lynch syndrome tests showed an inverse relationship between the percentage of mutation detected and the absolute number of tests performed over the time (overall Cochran-Armitage test for trend: P < 0.001). In families with BRCA1/2 or MMR identified mutations, there was an average number of 2.94 and 3.28 relatives performing targeted tests, respectively. This nationwide study shows a lack of referral and genetic testing in Lynch as compared to HBOC syndromes. Only a third of relatives of a proband with a predisposing mutation performed a targeted test. Enhanced information about benefit of genetic testing should be given to clinicians and patients for Lynch syndrome and relatives of a proband carrying an identified predisposing mutation.
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Proteínas Adaptadoras Transductoras de Señales/genética , Neoplasias de la Mama/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Proteínas de Unión al ADN/genética , Genes BRCA1 , Genes BRCA2 , Asesoramiento Genético/estadística & datos numéricos , Pruebas Genéticas/estadística & datos numéricos , Proteína 2 Homóloga a MutS/genética , Síndromes Neoplásicos Hereditarios/genética , Proteínas Nucleares/genética , Neoplasias Ováricas/genética , Derivación y Consulta/estadística & datos numéricos , Neoplasias de la Mama/prevención & control , Instituciones Oncológicas/estadística & datos numéricos , Neoplasias Colorrectales Hereditarias sin Poliposis/prevención & control , Reparación de la Incompatibilidad de ADN/genética , Análisis Mutacional de ADN/estadística & datos numéricos , Salud de la Familia , Femenino , Francia , Tamización de Portadores Genéticos , Asesoramiento Genético/tendencias , Pruebas Genéticas/tendencias , Humanos , Laboratorios/estadística & datos numéricos , Masculino , Homólogo 1 de la Proteína MutL , Mutación , Síndromes Neoplásicos Hereditarios/prevención & control , Neoplasias Ováricas/prevención & control , Derivación y Consulta/tendenciasRESUMEN
PURPOSE: In 1998 a translational research was initiated in Lyon aiming at identifying a prognostic "biomolecular signature" in rectal cancer. This paper presents the clinical outcome of the patients included in this study. PATIENTS AND METHODS: A total of 94 patients were included between 1998 and 2001. A staging with rectoscopy and biopsies was performed before treatment. In case of surgery, the operative specimen was analysed to evaluate the pathological response. There were two types of treatment: neoadjuvant radiotherapy (with or without concurrent chemotherapy) followed by surgery (76 cases) and radiotherapy alone with 'contactherapy' often associated with external beam radiotherapy (18 patients). RESULTS: The patients had a mean age of 63years. Stage was T1: 4, T2: 24, T3: 65 and T4: 1. The overall survival of the 94 patients was 62% at 8years with a rate of distant metastases of 29%. Rate of local recurrence at 8years was 6% in the neoadjuvant group and 16% in the radiotherapy group with an overall 8years survival in both groups respectively: 64% and 53%. There was a trend towards more metastases in cT3, tumour diameter above 4cm, circumferential extension. There was a significant increase in the risk of metastases for ypT3, ypN1-2 and Dworak score 1-2-3. In multivariate analysis ypT3 was significantly associated with a high rate of metastases (55%; P=0.0003). CONCLUSION: The rate of distant metastases is a major prognostic factor. These clinical results will serve as the base line to identify a "biomolecular signature" which could complement the TN(M) classification.
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Neoplasias del Recto/mortalidad , Neoplasias del Recto/terapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/mortalidad , Carcinoma/patología , Carcinoma/terapia , Quimioterapia Adyuvante , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Terapia Neoadyuvante , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Radioterapia Adyuvante , Neoplasias del Recto/patología , Medición de RiesgoAsunto(s)
Antígenos de Neoplasias/genética , Moléculas de Adhesión Celular/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Eliminación de Secuencia , Adulto , Anciano , Anciano de 80 o más Años , Reparación de la Incompatibilidad de ADN/genética , Molécula de Adhesión Celular Epitelial , Exones , Femenino , Pruebas Genéticas , Humanos , Masculino , Persona de Mediana Edad , Tasa de Mutación , Factores de RiesgoAsunto(s)
Poliposis Adenomatosa del Colon/genética , ADN Glicosilasas/genética , Reordenamiento Génico , Poliposis Adenomatosa del Colon/complicaciones , Poliposis Adenomatosa del Colon/etiología , Secuencia de Bases , Análisis Mutacional de ADN , Mutación de Línea Germinal , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Análisis de Secuencia por Matrices de Oligonucleótidos , Factores de RiesgoAsunto(s)
Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Mutación/genética , Proteínas Nucleares/genética , Proteínas Represoras/genética , Adulto , Anciano , Anciano de 80 o más Años , Hibridación Genómica Comparativa , Femenino , Humanos , Cariotipificación , Masculino , Persona de Mediana Edad , Nucleofosmina , Análisis de Secuencia por Matrices de Oligonucleótidos , Polimorfismo Genético , Pronóstico , Adulto Joven , Tirosina Quinasa 3 Similar a fms/genética , Proteínas ras/genéticaRESUMEN
Organised since 1990 in France, cancer genetics has been strengthened since 2003 by the programme "Plan Cancer" which resulted in an improvement of the organisation of activities. The aim of this review is to present an update of the estimation of the needs of the population in this field for the next ten years, provided by a group of experts mandated by the French National Cancer Institute. Identification and management of major hereditary predispositions to cancer have a major impact on decrease in mortality and incidence. Sensitivity of criteria for the detection of BRCA1/2 mutations could be substantially improved by enlarging the indication for genetic testing to isolated cases of ovarian cancer occurring before 70 years and to familial cases occurring after this age limit. In the Lynch syndrome, the present criteria would have an excellent sensitivity for the detection of mutations in the mismatch repair (MMR) genes if the pre-screening of tumours on microsatellite instability (MSI) phenotype was effective, but these criteria are actually poorly applied. However, genetic testing should not be proposed to all the patients affected by tumours belonging to the spectrum of major predispositions and a fortiori to unaffected persons unless an affected relative has been identified as a carrier. The prescription of tests should continue to be strictly controlled and organised, in patients as well as in at-risk relatives. The enlargement of criteria and the improvement in the spreading of recommendations should result in an increase of genetic counselling activity and of the prescriptions of tests by a factor 2 to 4, and to a lesser extent in the clinical management of at risk persons. In a near future, it appears important to mandate experts on specific issues such as the determinants of the lack of effective application of tumour screening for MSI phenotype, the recommendations for the identification and the management of MYH-associated polyposis, or the predictive value of tumour characteristics for the identification of BRCA1/2 mutations. The expected increase in cancer genetics activity will need an optimal organisation to increase the throughput. Such measures will help in facing up to new predispositions that will probably be identified in common cancers.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Pruebas Genéticas , Necesidades y Demandas de Servicios de Salud , Neoplasias/genética , Factores de Edad , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Neoplasias de la Mama/prevención & control , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/prevención & control , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Femenino , Predicción , Francia , Genes BRCA1 , Genes BRCA2 , Pruebas Genéticas/psicología , Necesidades y Demandas de Servicios de Salud/organización & administración , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Necesidades y Demandas de Servicios de Salud/tendencias , Humanos , Masculino , Mutación , Neoplasias/diagnóstico , Neoplasias/prevención & control , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , Neoplasias Ováricas/prevención & controlAsunto(s)
Proteínas Reguladoras de la Apoptosis/genética , Encéfalo/patología , Duramadre/patología , Hemangioma Cavernoso del Sistema Nervioso Central/genética , Hemangioma Cavernoso del Sistema Nervioso Central/patología , Proteínas de la Membrana/genética , Mutación/genética , Proteínas Proto-Oncogénicas/genética , Adulto , Estudios de Cohortes , Análisis Mutacional de ADN , Femenino , Marcadores Genéticos/genética , Predisposición Genética a la Enfermedad/genética , Pruebas Genéticas , Genotipo , Hemangioma Cavernoso del Sistema Nervioso Central/fisiopatología , Humanos , Masculino , Neoplasias Meníngeas/patología , Meningioma/patología , Persona de Mediana Edad , Sitios de Empalme de ARN/genéticaRESUMEN
The t(8;16)(p11;p13) is a rare translocation involved in de novo and therapy-related myelomonocytic and monocytic acute leukemia. It fuses two genes encoding histone acetyltransferases (HATs), MYST3 located at 8p11 to CREBBP located at 16p13. Variant translocations involve other HAT-encoding genes such as EP300, MYST4, NCOA2 or NCOA3. MYST3-linked acute myeloid leukemias (AMLs) share specific clinical and biological features and a poor prognosis. Because of its rarity, the molecular biology of MYST3-linked AMLs remains poorly understood. We have established the genome and gene expression profiles of a multicentric series of 61 M4/M5 AMLs including 18 MYST3-linked AMLs by using array comparative genome hybridization (aCGH) (n=52) and DNA microarrays (n=44), respectively. We show that M4/5 AMLs have a variety of rare genomic alterations. One alteration, a gain of the MYB locus, was found recurrently and only in the MYST3-linked AMLs (7/18 vs 0/34). MYST3-AMLs have also a specific a gene expression profile, which includes overexpression of MYB, CD4 and HOXA genes. These features, reminiscent of T-cell acute lymphoid leukemia (ALL), suggest the targeting of a common T-myeloid progenitor.
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Perfilación de la Expresión Génica/métodos , Genes myb/genética , Histona Acetiltransferasas/genética , Leucemia Mielomonocítica Aguda/genética , Antígenos CD4/genética , Hibridación Genómica Comparativa , Regulación Neoplásica de la Expresión Génica , Genoma Humano , Proteínas de Homeodominio/genética , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas Proto-Oncogénicas c-myb/genéticaAsunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Mutación Missense , Factores de Transcripción NFI/genética , Proteínas de Neoplasias/genética , Mutación Puntual , Policitemia Vera/genética , Eliminación de Secuencia , Sustitución de Aminoácidos , Secuencia de Bases , Cromosomas Humanos Par 1/genética , Errores Diagnósticos , Progresión de la Enfermedad , Femenino , Genes Supresores de Tumor , Humanos , Janus Quinasa 2/genética , Leucemia Monocítica Aguda/genética , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Factores de Transcripción NFI/química , Proteínas de Neoplasias/química , Policitemia Vera/diagnóstico , Estructura Terciaria de Proteína/genética , Trombocitemia Esencial/diagnósticoRESUMEN
The Hereditary Non-Polyposis Colorectal Cancer syndrome (HNPCC) has initially been described as a predisposition to colorectal cancers (CRC). Subsequently, other cancers, such as endometrial cancers (EC), have been added. The objective of this review was to update data on endometrial cancers of HNPCC syndrome. Endometrial cancers of the HNPCC syndrome are characterized by a younger age at diagnosis (46-48 year old), and a higher cumulative risk along life (30% at 70 years). Complex atypical hyperplasia seems to occur before the cancer, but the transition between precursors and cancer seems to be short. Histology of endometrial cancers of the HNPCC syndrome appears quite similar to that of sporadic cases, except for non-endometrioid lesions which seem more frequent and could occur in younger women. Screening of endometrial cancer in predisposed women should associate annual clinical examination, transvaginal sonography and endometrial sampling. Unfortunately, available data on screening by sonography show that this test seems poorly accurate, with no asymptomatic cancer or hyperplasia recognized and interval cancers between screenings. Endometrial biopsy appears as the most interesting method, since 11 asymptomatic cancers and 14 hyperplasia have been diagnosed in 175 mutation carriers. Diagnostic hysteroscopy seems also interesting, but requires further evaluation. Prophylactic hysterectomy confers a complete protection against endometrial cancer. However, perioperative morbidity (especially in women with history of colorectal surgery) and long-term effects of ovarian suppression should also be considered. Screening of endometrial cancer remains the main objective of the management of those patients. Endometrial biopsy should have a larger place.
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Biopsia , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Neoplasias Endometriales/patología , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/cirugía , Hiperplasia Endometrial/patología , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/genética , Neoplasias Endometriales/cirugía , Femenino , Asesoramiento Genético , Predisposición Genética a la Enfermedad , Humanos , Histerectomía , Histeroscopía , Tamizaje Masivo , Prevención Primaria/métodos , Resultado del TratamientoRESUMEN
The objective of this study was to report the value of diagnostic hysteroscopy and endometrial biopsy for the detection of complex atypical hyperplasia or cancer in asymptomatic human non-polyposis colon cancer (HNPCC) patients. The secondary objective was to evaluate the accuracy of hysteroscopy, using endometrial biopsy as a gold standard. Consecutive patients at risk of HNPCC evaluated between January 1, 1999, and June 30, 2006 were included if they underwent diagnostic hysteroscopy at least once. Patients with a history of hysterectomy and those unwilling to undergo diagnostic hysteroscopy were not included. Yearly follow-up evaluations included diagnostic hysteroscopy, with endometrial biopsy. Hysteroscopic and histologic findings were recorded and compared. We included 62 patients, of whom 13 had mismatch repair gene mutations and 49 met Amsterdam II criteria. Of 125 attempted hysteroscopies, 11 (8%) failed. Hysteroscopy showed normally appearing mucosa in 46 cases, nonmalignant lesions in 65 cases, and possibly malignant lesions in 3 cases with abnormal uterine bleeding. Endometrial biopsy was attempted in 116 cases and failed in 12 (10%). Three cases each of simple hyperplasia and of cancer were diagnosed. No preinvasive or invasive lesions were found in asymptomatic women. When compared to endometrial biopsy, sensitivity of hysteroscopy was 100% for the detection of hyperplasia or cancer. No cases of cancer were diagnosed in asymptomatic patients in our study. However, diagnostic hysteroscopy ensured the diagnosis of endometrial adenocarcinoma in HNPCC women with bleeding. Nevertheless, usefulness and optimal modalities of screening remain to be determined.
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Neoplasias del Colon/complicaciones , Histeroscopía , Enfermedades Uterinas/complicaciones , Enfermedades Uterinas/diagnóstico , Pólipos Adenomatosos , Adulto , Biopsia/estadística & datos numéricos , Femenino , Humanos , Estudios Prospectivos , Factores de Riesgo , Enfermedades Uterinas/cirugíaAsunto(s)
Cromosomas Humanos Par 16/ultraestructura , Cromosomas Humanos Par 8/ultraestructura , Histona Acetiltransferasas/genética , Leucemia Monocítica Aguda/genética , Fusión de Oncogenes , Proteínas de Fusión Oncogénica/genética , Transactivadores/genética , Translocación Genética , Anciano , Secuencia de Aminoácidos , Secuencia de Bases , Cromosomas Humanos Par 16/genética , Cromosomas Humanos Par 8/genética , Exones/genética , Resultado Fatal , Femenino , Regulación Leucémica de la Expresión Génica/genética , Regulación Leucémica de la Expresión Génica/fisiología , Histona Acetiltransferasas/química , Histona Acetiltransferasas/fisiología , Humanos , Intrones/genética , Datos de Secuencia Molecular , Coactivador 3 de Receptor Nuclear , Proteínas de Fusión Oncogénica/química , Estructura Terciaria de Proteína , Transactivadores/química , Transactivadores/fisiología , Transcripción GenéticaRESUMEN
INTRODUCTION: Germline mutations in the NF2 gene are responsible for 80 p.cent of neurofibromatosis type 2 typical cases. Mutations are mainly truncating mutations or deletions, missense mutations having been reported in few cases. An important phenotypic variability is observed among gene carriers. To assess whether the phenotypic variability of neurofibromatosis 2 could be linked to genotype, clinical data of 154 patients whose NF2 germline alteration had been identified in our laboratory have been collected. METHODS: A retrospective questionnaire was sent to the physicians in charge of these patients. Statistical analyses regarding genotypic and phenotypic data were performed by comparisons of average values and correlation tests. RESULTS: In French patients, type of mutation was correlated neither with patients' sex, nor with disease occurrence mode (de novo or inherited mutation). Disease associated with missense mutations occurred later, with a less severe symptomatology. Patients with nonsense or frameshift mutations were more frequently affected with meningiomas and spinal tumours, in addition to VIII nerve schwannomas, an observation that underlies the genetic determination of the number and type of NF2-related tumours. CONCLUSION: Results from the literature as well as from our study tend to show that only few correlations exist between genotype and phenotype in the NF2 disease. It also recognizes that missense mutations have a lower level of evolution, severity and mortality risk. Nonsense and frameshift mutations seem to be associated with a higher number of meningiomas and spinal tumours. Therefore, NF2 gene screening keeps its indications in both typical and moderate forms of the disease. Mutations are responsible of 80 p.cent of typical forms; in moderate forms, identification of a missense mutation seems linked to a lower disease evolution. In any case, assessment and supervision should be identical. Finally, in a small number of cases, the NF2 gene appears to be implicated in clinical forms different from those defined by NIH and it might be of interest to enlarge the clinical features suggestive of the disease.
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Genes de la Neurofibromatosis 2/fisiología , Heterocigoto , Neurofibromatosis 2/genética , Neurofibromatosis 2/fisiopatología , Adulto , Codón sin Sentido/genética , Codón sin Sentido/fisiología , Femenino , Mutación del Sistema de Lectura/genética , Mutación del Sistema de Lectura/fisiología , Francia/epidemiología , Genotipo , Humanos , Masculino , Meningioma/epidemiología , Meningioma/etiología , Meningioma/genética , Mutación Missense/genética , Mutación Missense/fisiología , Neurofibromatosis 2/epidemiología , Fenotipo , Médicos , Estudios Retrospectivos , Medición de Riesgo , Neoplasias de la Columna Vertebral/epidemiología , Neoplasias de la Columna Vertebral/etiología , Neoplasias de la Columna Vertebral/genética , Encuestas y CuestionariosAsunto(s)
Perfilación de la Expresión Génica , Regulación Leucémica de la Expresión Génica/genética , Leucemia Mielomonocítica Crónica/diagnóstico , Leucemia Mielomonocítica Crónica/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Leucocitos/citología , Masculino , Persona de Mediana Edad , Modelos Genéticos , Mutación , Análisis de Secuencia por Matrices de OligonucleótidosRESUMEN
Turcot syndrome is clinically characterized by the occurrence of primary brain tumor and colorectal tumor and has, in previous reports, been shown associated with germline mutations in the genes APC, MLH1, MHS6, and PMS2. To date, only few families have been documented by molecular analysis. We report two new families with Turcot syndrome to illustrate and review its characteristics and facilitate diagnosis. Molecular analysis revealed two germline mutations, one in the MLH1 gene and one in MSH2. The latter has never been describe in the literature. Personal and familial relevant anamnestic data from patients with glioma might aid in the diagnosis of genetic disorders. The subsequent molecular characterization may contribute to the appropriate care of affected patients and asymptomatic gene carriers.
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Proteínas Adaptadoras Transductoras de Señales/genética , Neoplasias Encefálicas/genética , Neoplasias Colorrectales/genética , Predisposición Genética a la Enfermedad , Proteína 2 Homóloga a MutS/genética , Proteínas Nucleares/genética , Anciano , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Análisis Mutacional de ADN , Femenino , Mutación de Línea Germinal , Humanos , Inmunohistoquímica , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Homólogo 1 de la Proteína MutL , LinajeRESUMEN
AIMS: Clusterin is a sulphated glycoprotein, implicated in many processes, including tumorigenesis. Several studies have reported its overexpression in many human neoplasms, including prostatic and pancreatic adenocarcinoma, but its expression has not been described previously in other pancreatic tumours. Our aim was to investigate the expression of clusterin by immunohistochemistry in 30 endocrine pancreatic tumours (ENTs) and 22 solid pseudopapillary tumours (SPPTs) to document its potential in differential diagnosis, and the possible correlation between this expression and clinicopathological parameters. METHODS AND RESULTS: Cytoplasmic positivity was scored qualitatively (weak, moderate or strong immunoreactivity) and quantitatively on a four-tiered scale. The pattern of immunoreactivity (cytoplasmic, secretory or Golgi pattern) was also assessed. Except for scattered tumour cells in five cases, all SPPTs were negative, while all ENTs showed strong immunoreactivity in a variable proportion of tumour cells. Neither the reactivity score nor the pattern of immunoreactivity was correlated with tumour size, vascular permeation, perineural invasion or lymph node metastasis. DISCUSSION: The expression of clusterin in all ENTs is of interest and could be an additional useful marker in the differential diagnosis with SPPTs. However, the lack of correlation between clusterin expression and clinicopathological parameters rules out a role as a predictive marker for endocrine tumour aggressiveness.