1/75. neuroblastoma in two siblings supports the role of 1p36 deletion in tumor development.Familial neuroblastoma occurs rarely. We studied a family with three children; one of them has a disseminated (stage 4) and another has a localized (stage 2) neuroblastoma. We observed subtelomeric locus D1Z2 (1p36) deletion in both tumors by using double-color fluorescence in situ hybridization. The MYNC gene was found in single copy in both tumors. loss of heterozygosity (LOH) and restriction fragment length polymorphism analyses were performed by using DNA from frozen tumor cells and from microdissected tumor areas excised from paraffin-embedded sections. We detected somatic LOH at locus D1S468 (1p36) in a tumor-cell population with a trisomy 1 of the stage-2 patient. neuroblastoma cells of the stage-4 patient were diploid and showed allelic loss at the following loci: D1S172, D1S80, D1S94, D1S243, D1S468, D1S214, D1S241, and D1S164. Haplotype study showed that the siblings inherited the same paternal 1p36-->pter chromosome region by homologous recombination and that, in the two tumors, arm 1p of different chromosomes of maternal origin was damaged. Our results suggest that the siblings inherited the predisposition to neuroblastoma associated with paternal 1p36 region and that tumors developed as a consequence of somatic loss of the maternal 1p36 allele.- - - - - - - - - - ranking = 1keywords = situ (Clic here for more details about this article) |
2/75. schizophrenia - A disturbance of signal interaction between the entorhinal cortex and the dentate gyrus? The contribution of experimental dibenamine psychosis to the pathogenesis of schizophrenia: A hypothesis.In addition to the existence of complex memory (similar to the implicit nondeclarative memory of Squire), the existence of a phylogenetically old apparatus of a memory of situations (SMA) is supposed, which is to some extent comparable with the declarative memory of Squire. During actual sensory information the SMA generates a general frame and forms a general 'mark', indicating whether a given information has its origin inside or outside the body, and whether it is new or known. The procedure of this marking process can be explained as the time-depending arrest of a copy of the actual original information-transporting signal 'shower'; this copy must last until the feedback from thalamocortical centers indicates the termination of the processing of the original signal showers. The arrest of the shower copies is the performance of neuronal networks of the entorhinal cortex (EC) and the gyrus dentatus (GD). The psychopathological and biochemical analyses of experimental dibenamine psychosis show a different effect of dibenamine on the noradrenaline (NA) receptors of the EC and GD, respectively: these effects are responsible for the repeated perception cycles of a single situation. N,N-Dibencylamine blocks the postsynaptic alpha(1)-receptors of the EC without influencing the beta-receptors of the GD. Thus the interaction between EC and GD is changed: instead of new scenes, perceptions that have just been experienced get repeated presence and the quality of familiarity. The prolonged arrest of shower copies simultaneously blocks the entrance of new signal showers from the EC to the GD. No information-transporting signal showers can come in as long as the arrest lasts. In case of a disturbance in NA-dependent actions within the EC and the GD, the duration of arrest of information-transporting signal showers is shortened. Thus the formal frame of experience receives the quality of novelty instead of familiarity, and in addition the qualities of uncertainty, vagueness, and alienity. These very changes in perception and experience represent the basic disturbance of schizophrenia. All the symptoms of schizophrenia may be explained by this basic disturbance. The analysis of biochemical aspects turns attention to the energetic situation of NA and N-methyl-D-aspartate systems. These considerations suggest a genetic background of the basic disturbance of schizophrenia: transmitter effects on membranes of neurons and possibly also on glial cells, and energy supply of these effects may be predetermined genetically. It may be assumed that the compensation of such membrane-dependent disturbances will be possible within wide areas of the neural network, except for the 'bottleneck' of the overlapping region of the iso- and allocortex.- - - - - - - - - - ranking = 3keywords = situ (Clic here for more details about this article) |
3/75. Multiple basal cell carcinomas in a patient with acute myeloid leukaemia and chronic lymphocytic leukaemia.skin cancer is a well-recognized risk of prolonged immunosuppression, for example, following renal transplantation. These tumours contrast with idiopathic lesions in that squamous cell, rather than basal cell carcinomas usually predominate. We report a Caucasian female who developed multiple basal cell carcinomas following protracted cytotoxic therapy for acute myeloid leukaemia and subsequently chronic lymphocytic leukaemia. No other clinical risk factors nor relevant polymorphisms of genes encoding for detoxifying enzymes were identified. Immune suppression is a well-recognized cause of multiple skin tumours, the most striking increase usually being of squamous cell carcinomas. We believe this woman is representative of a subgroup of immunosuppressed patients who, for as yet poorly understood reasons, have a predisposition to basal cell, rather than squamous cell carcinoma accrual.- - - - - - - - - - ranking = 1822.9149790815keywords = carcinoma (Clic here for more details about this article) |
4/75. Type 2 segmental darier disease.A 45-year-old man had bilateral disseminated involvement of darier disease, and two of his sisters likewise had lesions suggesting this trait. Remarkably the propositus showed, in addition, a unilateral, systematized, segmental pattern of excessively pronounced Darier lesions. This unusual case can be taken as an example of type 2 segmental darier disease. In contrast to the type 1 segmental manifestation that develops from a new mutation occurring in an otherwise healthy embryo, the type 2 segmental involvement would originate in a heterozygous embryo from postzygotic loss of the corresponding normal allele, resulting in a cell clone that is either homozygous or hemizygous for the mutation. This concept would explain why the segmental lesions were excessively pronounced and superimposed on the ordinary trait. Future studies may show whether the concept of type 2 segmental darier disease can be confirmed at the molecular level.- - - - - - - - - - ranking = 1keywords = situ (Clic here for more details about this article) |
5/75. Hepatocellular carcinoma arising in the absence of cirrhosis in genetic haemochromatosis: three case reports and review of literature.Genetic haemochromatosis constitutes a high risk factor for the development of hepatocellular carcinoma. It is widely accepted that venesection prevents the evolution of cirrhosis in haemochromatosis and indirectly protects against the development of hepatocellular carcinoma. Clinical, pathological and radiological data are presented on three patients who did not conform to the 'siderosis-cirrhosis-carcinoma' sequence and in whom prompt and adequate iron depletion did not prevent the development of cancer. This is the first report of hepatocellular carcinoma intervening in non-cirrhotic liver in two siblings with genetic haemochromatosis. The current literature on the subject is reviewed. The direct oncogenic role of iron remains to be elucidated. Hepatocellular carcinoma should be considered as a differential diagnosis in patients with non-cirrhotic genetic haemochromatosis who present with clinical deterioration during the course of an otherwise uneventful venesection programme.- - - - - - - - - - ranking = 2050.7793514667keywords = carcinoma (Clic here for more details about this article) |
6/75. Endometrial carcinoma in tamoxifen-treated breast cancer patient: clinicopathological, immunohistochemical, and genetic analysis.Endometrial polyps and endometrial neoplasms are a recognized complication of chronic tamoxifen treatment. This study describes an endometrial carcinoma that developed in a woman receiving low-dose tamoxifen treatment for breast cancer. Little is known about steroid receptor status, somatic alterations in oncogenes and tumor suppressor genes, and inherited susceptibility in endometrial carcinomas associated with tamoxifen use. In the present case, the endometrial carcinoma was negative for estrogen receptors and weakly positive for progesterone receptors. In addition, analysis of K-ras, c-erbB2/neu, cyclin d1, and p53 status revealed a codon 12 point mutation in the K-ras oncogene. The patient was determined not to be a carrier of germ-line mutations in cytochrome P-450 1A1 (CYP1A1), an estrogen-metabolizing gene previously associated with enhanced endometrial cancer risk, but she was a carrier of a methylenetetrahydrofolate reductase gene variant related with putative alterations in dna methylation.- - - - - - - - - - ranking = 1595.0506066963keywords = carcinoma (Clic here for more details about this article) |
7/75. Genetic susceptibility for specific cancers. Medical liability of the clinician.The use of genetic profiling techniques to detect individuals with an increased susceptibility to heritable cancers has provoked recent legal interest in the duties of the attending physician and in the rights of patients and their families. In the current study specific prima facie and recently litigated cases are presented and explored to delineate the issues facing physicians and to illustrate the prerogatives of patients who are caught up in a heritable cancer enigma. Various courts have attempted to answer questions involving lawsuits in which incidents of breast/ovarian carcinoma and colon carcinoma have provoked claims of negligence against health care providers. health care workers involved in the care of these patients have specific duties to these individuals. It would appear that physicians are being forced to assume the additional duty of delving into a patient's family history of cancer through multiple generations. This duty is followed by a responsibility to provide detailed counseling to those patients in whom such activity impacts the diagnosis and management of familial cancer.- - - - - - - - - - ranking = 455.72874477039keywords = carcinoma (Clic here for more details about this article) |
8/75. Germline CDKN2A mutation implicated in predisposition to multiple myeloma.Germline mutations of the CDKN2A (p16(INK4A)) tumor suppressor gene predispose patients to melanoma and pancreatic carcinoma. In contrast, mutations of the murine CDKN2A gene predispose BALB/c mice to pristane-induced plasmacytoma. We describe here a family in which a germline mutation of CDKN2A is present in 4 individuals who developed melanoma as well as in a fifth family member who is suffering from multiple myeloma. To determine whether the CDKN2A mutation predisposed the myeloma patient to her disease, we carried out loss of heterozygosity studies on sorted bone marrow from this individual and observed loss of the wild type CDKN2A allele in the malignant plasma cells. We suggest that germline mutations of CDKN2A may predispose individuals to a wider variety of malignancy than has been hitherto reported, but that the expression of these cancers may depend heavily on the genetic background of the patient. (blood. 2000;95:1869-1871)- - - - - - - - - - ranking = 227.86437238519keywords = carcinoma (Clic here for more details about this article) |
9/75. Cytogenetic heterogeneity and clonal evolution in synchronous bilateral breast carcinomas and their lymph node metastases from a male patient without any detectable BRCA2 germline mutation.Two synchronous bilateral breast carcinomas and their matched lymph node metastases from a 70-year-old man were cytogenetically analyzed. All four tumors were near-diploid, and except for the primary tumor from the right breast, had a 45,X,-Y clone in common. The loss of the y chromosome was, however, common to all four tumors, whereas metaphase cells from peripheral blood lymphocytes showed a normal 46, XY chromosome complement. The primary tumor from the right breast was monoclonal, with loss of the y chromosome and gain of 1q, whereas its metastasis had two related clones: the 45,X,-Y clone, and the other a more complex version of the clone in the primary tumor, with inv(3), -14, and del(16)(q13) as additional changes. The primary tumor from the left breast was polyclonal with three unrelated clones: 45,X,-Y/45,XY,-18/47,XY, 20, two of which were present in its metastasis. DNA flow cytometric studies showed diploidy for both primary tumors. No mutation in the BRCA2 gene was found on analysis of DNA from peripheral blood lymphocytes. The present findings show that del(16)(q13) is a recurrent finding among male breast carcinomas and that some of the primary cytogenetic abnormalities, as well as the pattern of chromosomal changes during the progression of sporadic breast carcinoma in the male, are similar to those in the female. In addition, the loss of the y chromosome in the tumors but not in peripheral blood lymphocytes, suggests a possible role for this abnormality in the pathogenesis of male breast carcinoma.- - - - - - - - - - ranking = 1822.9149790815keywords = carcinoma (Clic here for more details about this article) |
10/75. Clear cell carcinoma of the fimbria of the fallopian tube in a BRCA1 carrier undergoing prophylactic surgery.We report the case history of a patient with a family history of breast and ovarian cancer who was subsequently found to be a carrier of the BRCA1 gene, in whom a tiny focus of clear cell carcinoma was found at the fimbrial end of one fallopian tube when she underwent prophylactic hysterectomy and bilateral salpingoophorectomy. The implications of this finding are discussed.- - - - - - - - - - ranking = 1139.321861926keywords = carcinoma (Clic here for more details about this article) |
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