1/64. Inherited cancer and the primary care physician. Barriers and strategies.Difficulties faced by primary care physicians as they increase their responsibility for the diagnosis of inherited cancer risk include issues of cognitive strategy, the context of care, and cultural and institutional factors. Charateristics common to many genetic disorders--such as rarity, variability, implications for relatives, and temporal pattern--render our usual cognitive strategies less effective. Constraints of managed care, care teams, and high turnover of panels create a particularly difficult context for the care of people at risk for inherited cancer. Echoes of the eugenics movement, the implications of expanding genetic knowledge, and concerns about discrimination all complicate collaborative clinical decision making. Eight strategies are suggested to cope with these barriers to diagnosis. Primary care physicians also face challenges managing patients identified as at increased risk for inherited cancer. These include confidentiality, coordination and communication. Concerns for protecting the patient's confidentiality can inadvertently leave primary care physicians with partial information. Coordination is complicated when multiple organ systems and individuals are at risk, and knowledgable specialty centers may be distant. communication requires sensitivity and skill in translating complex concepts from molecular biology and statistics into lay terms. Seven strategies are suggested to help with management.- - - - - - - - - - ranking = 1keywords = cancer (Clic here for more details about this article) |
2/64. 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 = 0.30215647427916keywords = cancer, germ (Clic here for more details about this article) |
3/64. Evidence for a recessive inheritance of Turcot's syndrome caused by compound heterozygous mutations within the PMS2 gene.Turcot's syndrome is a genetic disease characterized by the concurrence of primary brain tumors and colon cancers and/or multiple colorectal adenomas. We report a Turcot family with no parental consanguinity, in which two affected sisters, with no history of tumors in their parents, died of a brain tumor and of a colorectal tumor, respectively, at a very early age. The proband had a severe microsatellite instability (MIN) phenotype in both tumor and normal colon mucosa, and mutations in the TGFbeta-RII and APC genes in the colorectal tumor. We identified two germline mutations within the PMS2 gene: a G deletion (1221delG) in exon 11 and a four-base-pair deletion (2361delCTTC) in exon 14, both of which were inherited from the patient's unaffected parents. These results represent the first evidence that two germline frameshift mutations in PMS2, an MMR gene which is only rarely involved in HNPCC, are not pathogenic per se, but become so when occurring together in a compound heterozygote. The compound heterozygosity for two mutations in the PMS2 gene has implications for the role of protein PMS2 in the mismatch repair mechanism, as well as for the presymptomatic molecular diagnosis of at-risk family members. Furthermore, our data support and enlarge the notion that high dna instability in normal tissues might trigger the development of cancer in this syndrome.- - - - - - - - - - ranking = 0.4450136171363keywords = cancer, germ (Clic here for more details about this article) |
4/64. Novel germline mutation (300-305delAGTTGA) in the human MSH2 gene in hereditary non-polyposis colorectal cancer (HNPCC).Hereditary non-polyposis colorectal cancer (HNPCC) is a common hereditary syndrome characterized by the high incidence and early onset of colorectal cancer. The majority of the HNPCC families carry germline mutations in either the MSH2 or the MLH1 mismatch repair gene. A 46 year-old female patient whose family history fulfilled the Amsterdam criteria for HNPCC was diagnosed with undifferentiated adenocarcinoma of the transverse colon. Recognizing the Lynch 2 syndrome (the existance of multiple HNPCC related cancers in a pedigree), we used polymerase chain reaction followed by direct sequencing to screen the coding regions of both the MSH2 and the MLH1 genes for germline mutations in dna from the patient. We detected a novel germline mutation (300-305delAGTTGA) in exon 2 of human MSH2. We noted microsatellite instability in four microsatellite loci. immunohistochemistry showed a lack of expression of the MSH2 gene product in the tumor, suggesting that the mutation is a disease-causing mutation. copyright Wiley-Liss, Inc.- - - - - - - - - - ranking = 1.557547659977keywords = cancer, germ (Clic here for more details about this article) |
5/64. Hereditary cancers in children and ethical and psychosocial implications.This article describes the application of genetic testing of children for hereditary cancers and the resultant ethical and psychosocial implications. Basic cancer genetics concepts are reviewed. Specific hereditary cancers that may affect children are described along with case examples and recommendations for nursing practice.- - - - - - - - - - ranking = 1keywords = cancer (Clic here for more details about this article) |
6/64. Malignant cylindroma in Brooke-Spiegler syndrome.A 68-year-old female patient presented with a history of gradual appearance of multiple nodules situated predominantly on the scalp and neck, with a few nodules on the trunk. The nodules began to appear at the age of 30. family history revealed that the patient's brother, son, father and grandmother had similar cutaneous lesions. The dominant histopathological pattern was that of a cylindroma. Features of both cylindroma and spiradenoma (spiradenocylindroma) were present within the same lesion in some biopsies. Most lesions on the scalp were skin-colored with a smooth surface. The largest tumors located on the neck were tender and ulcerated. Histopathologically, these tumors had the morphology of a high-grade malignant solid neoplasm with epithelioid features.- - - - - - - - - - ranking = 0.022957726654336keywords = neoplasm (Clic here for more details about this article) |
7/64. Molecular pathologic analysis enhances the diagnosis and management of muir-torre syndrome and gives insight into its underlying molecular pathogenesis.The muir-torre syndrome (MTS) is an autosomal dominantly inherited disorder, characterized by visceral malignancies and sebaceous skin lesions. In a subset of MTS families the disease is due to an underlying dna mismatch-repair defect. We have identified a MTS family whose spectrum of reported neoplasia included adenocarcinomas of numerous gastrointestinal sites, carcinomas of the endometrium, ovary and breast, papillary transitional cell carcinoma of the ureter, a range of cutaneous tumors, as well as keratoacanthomas. All tumors were tested for microsatellite instability and immunohistochemically stained for expression of MLH1 and MSH2 proteins. All tumors were found to be microsatellite unstable and lacking in MSH2 protein expression. The subsequent mutation detection focused on hMSH2, and a germline mutation was identified (CAA-->TAA, Gln-->STOP, codon 337). This mutation was subsequently found in a family member with a single skin lesion only. We propose that the combination of immunohistologic and microsatellite instability analysis can be exploited to screen individuals with characteristic skin lesions even before development of visceral tumors and to direct the subsequent germline mutation search. The profile of microsatellite instability and the genes rendered dysfunctional differed between tumor samples, suggesting that the molecular pathogenesis varied between lesions, despite a common germline mutation.- - - - - - - - - - ranking = 0.23894899713302keywords = germ (Clic here for more details about this article) |
8/64. risk in numbers--difficulties in the transformation of genetic knowledge from research to people--the case of hereditary cancer.Difficulties in communicating diagnostic information are exacerbated when the 'diagnosis' is a 'genetic risk' for cancer. The risk estimation demanded in this situation differs from other types of probability estimations. Observations of participants in 45 consultation sessions between physicians and potential patients were conducted at a clinic for hereditary cancer to explore the communication of genetic information. Thirty-three sessions were audiotaped, transcribed verbatim and analyzed, along with notes from the other sessions. A dominant theme was found to be numerical discussion of risk. Further analysis resulted in the description of problems for practitioners in the process of translating scientific knowledge into clinical management. Problems in providing information include unclear aims of the consultation sessions, mixing various types of background information and probabilities, recognizing how low the predictive values are, and difficulties in communicating the relationship between probability and conclusions. Problems in communicating information about the genetic risk for cancer are of at least two types: dilemmas arising from uncertainties implicit in the nature of the information itself and difficulties in communicating information in a manner that those concerned can interpret. These issues need clarification, so that information with far-reaching consequences can be made as clear and comprehensible as possible for those involved.- - - - - - - - - - ranking = 1keywords = cancer (Clic here for more details about this article) |
9/64. No BRCA1 germline mutation in a family with uterine papillary serous carcinoma: a case report.The purpose of the study was to examine BRCA1 germline mutation and its relationship to BRCA1 expression in two patients, a mother and a daughter, both diagnosed with uterine papillary serous carcinoma (UPSC). dna was screened for BRCA1 and BRCA2 germline mutations common in the Jewish population (185delAG, 5382insC, and 6174delT) by PCR-based assay and with a protein truncation test (PTT) to detect mutation in exon 11 of BRCA1 and exons 10 and 11 of BRCA2. BRCA1 expression in fixed tumor tissues was assessed by immunocytochemistry (IHC). No germline mutation in either BRCAI or BRCA2 gene was found in the two patients. Both samples showed reduced levels of BRCAI expression. Taken together, these results suggest that undetected or unscreened for germline mutation may be associated with occurrence of this rare tumor type in two members of the same family. Alternatively, an epigenetic mechanism such as BRCA1 promoter hypermethylation may be responsible for reduced expression of BRCA1 in the absence of dna mutations.- - - - - - - - - - ranking = 0.63719732568805keywords = germ (Clic here for more details about this article) |
10/64. Multiple fibroadenomas harbouring carcinoma in situ in a woman with a family history of breast/ovarian cancer.A 46 year old woman with a family history of breast and ovarian cancer presented with multiple fibroadenomas in both breasts. From three fibroadenomas removed from the left breast carcinoma in situ (CIS) had developed. One fibroadenoma gave rise to ductal CIS, whereas the other two harboured lobular CIS. This is the first report of three fibroadenomas simultaneously giving rise to CIS. In addition, synchronous fibroadenomas harbouring different types of CIS from one fibroadenoma to the other have never been described. Direct sequencing revealed a mutation (5075G-->A) in the BRCA1 gene, but retention of BRCA1 immunohistochemical staining and no loss of heterozygosity at the BRCA1 locus by polymerase chain reaction made a pathogenic mutation in BRCA1 unlikely. Furthermore, in this family no cosegregation of breast cancer with this BRCA1 mutation was seen. Indeed, this mutation is now regarded as a polymorphism. This case stresses the need for histological evaluation of all breast masses in women with a strong positive family history for breast and/or ovarian cancer.- - - - - - - - - - ranking = 1keywords = cancer (Clic here for more details about this article) |
| | Next -> |