1/90. Molecular assessment of clonality leads to the identification of a new germ line TP53 mutation associated with malignant cystosarcoma phyllodes and soft tissue sarcoma.Cystosarcoma phyllodes (CSP) is a rare breast neoplasm composed of stromal and epithelial elements. It usually runs a benign course but it may metastasize. In a 31-year-old patient with recurring CSP, a mesenchymal tumor in the leg developed. The question arose whether the latter tumor could be a metastasis from the CSP, which would have major treatment consequences. The problem was addressed using molecular methods, i.e., comparison of the pattern of polymorphic repeat markers on chromosome 17p as well as single strand conformation polymorphism analysis and sequencing of exons 5 to 8 of the TP53 gene in both tumor and normal tissue. An identical pattern of loss of heterozygosity in both breast tumors was demonstrated, but a different pattern was shown in the tumor in the leg. This led to the conclusion that the latter tumor had to be a new primary tumor. A mutation in codon 162 of the TP53 gene was found in the tumor tissue as well as in the normal tissue of this patient. This germ line mutation leads to the replacement of isoleucine by asparagine and most likely has functional consequences. In all four examined tumors of this patient, the normal TP53 allele was lost. This is strong evidence that this germ line TP53 mutation causes the genesis of these two rare primary mesenchymal tumors in this young patient. The current study exemplifies the power of molecular diagnostic methods in investigating the specific clinical problem of clonal relation between two separate tumors. The germ line mutation found in codon 162 of the TP53 gene and the association with cystosarcoma phyllodes have not been described previously.- - - - - - - - - - ranking = 1keywords = neoplasm (Clic here for more details about this article) |
2/90. Rectal cancer in a 13-year-old boy without a detectable germline mutation in FAP and HNPCC genes.Hereditary non-polyposis colorectal cancer (HNPCC) is characterized by familial clustering and early onset. It is unclear, however, whether the early onset of colorectal cancer necessarily represents HNPCC. A 13-year-old patient had rectal cancer and underwent curative surgery. DNA from this patient was examined for replication errors (RER) and genes related to familial colorectal cancer (APC, hMSH2, and hMLH1). The patient had a negative family history of colorectal cancer, did not show the RER phenotype, and had no germline mutation of the APC, hMSH2, and hMLH1 genes. The present case suggests that an unusually young patient with colorectal cancer is not always an HNPCC proband. observation over time, however, will be needed, as a first mutator of familial colorectal cancer could be missed.- - - - - - - - - - ranking = 7938.8593197463keywords = cancer (Clic here for more details about this article) |
3/90. 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 = 721.7144836133keywords = cancer (Clic here for more details about this article) |
4/90. Genetic instability did not lead to p53 mutations in an extremely early-onset breast cancer in a cancer-prone family.BACKGROUND: A positive family history is a major contributor to risk of development of breast cancer. methods: Somatic and germ line mutations of p53 and genetic instability were evaluated for an extremely early-onset breast cancer case in a cancer-prone family. RESULTS: The mode of inheritance in this case was clearly autosomal dominant. dna replication error was recognized by detecting microsatellite allelic alterations. However, mutations of p53 were not found at either somatic or germ-line level. CONCLUSION: These genetic studies suggest that an increased genetic instability did not lead to p53 gene mutations in this breast cancer patient.- - - - - - - - - - ranking = 8660.5738033596keywords = cancer (Clic here for more details about this article) |
5/90. 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 = 721.7144836133keywords = cancer (Clic here for more details about this article) |
6/90. 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 = 4331.2869016798keywords = cancer, neoplasm (Clic here for more details about this article) |
7/90. Familial mixed tumors of the parotid gland.BACKGROUND: The most common neoplasm of the parotid gland is the pleomorphic adenoma. The familial occurrence of such tumors arising within the parotid gland is rare, with only 3 previous reports in the literature. Bilateral synchronous pleomorphic adenomas of the parotid gland are also uncommon. We report 2 siblings with pleomorphic adenomas of the parotid gland, 1 of whom had bilateral synchronous mixed tumors. patients and methods Chromosomal analysis of tumor cells from the sibling with bilateral adenomas revealed the translocation t(3;12)(p21;q15). Chromosome 12q breakpoints have previously been identified in a wide variety of solid tumors including pleomorphic adenomas of the parotid gland. CONCLUSIONS: We discuss bilateral mixed tumors, familial parotid tumors, and the potential for a genetic predisposition for the recurrence of such parotid tumors, as suggested by characteristic chromosomal translocations associated with mixed tumors.- - - - - - - - - - ranking = 1keywords = neoplasm (Clic here for more details about this article) |
8/90. 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 = 5773.7158689064keywords = cancer (Clic here for more details about this article) |
9/90. 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 = 721.7144836133keywords = cancer (Clic here for more details about this article) |
10/90. 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 = 721.7144836133keywords = cancer (Clic here for more details about this article) |
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