National Cancer Institute®
Last Modified: June 1, 2002
UI - 11894916
AU - Wiedemann LM; Burns JH; Birnie GD
TI - Differences among the polyadenylated RNA sequences of human leucocyte populations: an approach to the objective classification of human leukaemias.
SO - EMBO J 1983;2(1):9-13
AD - The Beatson Institute for Cancer Research, Bearsden, Glasgow, UK.
We have constructed a complementary DNA (cDNA) library representing expressed sequences of the white blood cells from a patient with chronic granulocytic leukaemia. The library was screened by colony hybridization of 32P-labelled cDNAs synthesized from the polyadenylated RNAs of the white blood cells from patients with chronic granulocytic or chronic lymphocytic leukaemia. The autoradiographic patterns were compared and 70 recombinants were selected to comprise a panel which distinguished between these two types of leukaemia. Hybridization of this panel with complementary DNAs transcribed from the polyadenylated RNAs of a variety of normal and neoplastic leucocyte populations showed that the RNA sequences in high abundance in leucocytes from chronic granulocytic leukaemias differ quite radically from those in other leucocytes. The patterns of hybridization seen when this panel was challenged with cDNAs representing the RNAs of normal and leukaemic leucocyte populations were sufficiently different to distinguish clearly the peripheral blood leucocytes of chronic granulocytic leukaemias from other populations of white blood cells, both normal and leukaemic. We suggest that this approach might provide additional markers useful in the classification of the acute leukaemias, especially the undifferentiated leukaemias whose identification by conventional methods is uncertain.
UI - 11819819
AU - Yu ZC; Ding J; Nie YZ; Fan DM; Zhang XY
TI - Preparation of single chain variable fragment of MG(7) mAb by phage display technology.
SO - World J Gastroenterol 2001 Aug;7(4):510-4
AD - Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
AIM: To develop the single chain variable fragment of MG MG(7)murine anti-human gastric cancer monoclonal antibody using the phage display technology for obtaining a tumor-targeting mediator. METHODS: mRNA was isolated from MG MG(7) producing murine hybridoma cell line and converted into cDNA. The variable fragments of heavy and light chain were amplified separately and assembled into ScFv with a specially constructed DNA linker by PCR. The ScFvs DNA was ligated into the phagmid vector pCANTAB5E and the ligated sample was transformed into competent E. Coli TG1. The transformed cells were infected with M13K07 helper phage to form MG MG(7) recombinant phage antibody library. The volume and recombinant rate of the library were evaluated by means of bacterial colony count and restriction analysis. After two rounds of panning with gastric cancer cell line KATO III of highly expressing MG(7)-binding antigen, the phage clones displaying ScFv of the antibody were selected by ELISA from the enriched phage clones. The antigen-binding affinity of the positive clone was detected by competition ELISA. HB2151 E. Coli was transfected with the positive phage clone demonstrated by competition ELISA for production of a soluble form of the MG(7) ScFv. ELISA assay was used to detect the antigen-binding affinity of the soluble MG(7) ScFv. Finally, the relative molecular mass of soluble MG(7) ScFv was measured by SDS-PAGE. RESULTS: The V(H), V(L) and ScFv DNAs were about 340bp, 320bp and 750bp, respectively. The volume of the library was up to 2 X 10(6) and 8 of 11 random clones were recombinants. Two phage clones could strongly compete with the original MG(7) antibody for binding to the antigen expressed on KATO III cells. Within 2 strong positive phage clones, the soluble MG(7) ScFv from one clone was found to have the binding activity with KATO III cells. SDS-PAGE showed that the relative molecular weight of soluble MG(7) ScFv was 32. CONCLUSION: The MG(7) ScFv was successfully produced by phage antibody technology, which may be useful for broadening the scope of application of the antibody.
UI - 11348918
AU - Goel V
TI - Appraising organised screening programmes for testing for genetic susceptibility to cancer.
SO - BMJ 2001 May 12;322(7295):1174-8
AD - Department of Health Administration, McMurrich Building, Toronto, Ontario, Canada M5S 1A8. firstname.lastname@example.org
UI - 11676250
AU - Gar'kavtseva RF; Kazubskaia TP; Liubchenko LN; Kozlova SI; Belev NF;
TI - Sel'chuk VIu [Hereditary cancer: identification, genetic heterogeneity, medico-genetic consult]
SO - Vestn Ross Akad Med Nauk 2001;(9):27-33
The paper deals with a role of inherited factors responsible for the occurrence of malignant tumors. Inherited types of cancer are shown to occur virtually at its sites and averaged 5-15%. Formalized criteria for identifying inherited cancer diseases and their etiological and genetic heterogeneity are presented. A role of genes that genetically predispose to particular forms of cancer is shown, which allows for early (preclinical) diagnosis and prevention of cancer diseases.
UI - 11920200
AU - Badens C; di Montemuros FM; Thuret I; Michel G; Mattei JF; Cappellini
TI - MD; Lena-Russo D Molecular basis of haemoglobinopathies and G6PD deficiency in the Comorian population.
SO - Hematol J 2000;1(4):264-8
AD - Centre d'Enseignement et de Recherche en Genetique Medicale, Hopital d'enfants de la Timone, Marseilles, France. email@example.com
INTRODUCTION: The Comoro archipelago is characterised by a high prevalence of red cell genetic disorders such as G6PD deficiency and haemoglobinopathies, being a region endemic for malaria. Over the last 15 years, the city of Marseilles in France has become the main destination for Comorian immigrants. This Comorian community includes patients with sickle cell disease, sickle cell/beta-thalassaemia trait, thalassaemias and G6PD deficiency. MATERIALS AND METHODS: Allele frequencies for haemoglobin S, beta-thalassaemia and G6PD deficiency were determined from neonatal and prenatal screenings of the Comorian community. Haemoglobin fractions were detected by isoelectrofocalisation, and the quantitation of HbS, HbA, HbA(2) and HbF was performed by cation exchange high performance liquid chromatography. The molecular study involved 31 alleles carrying the betaS mutation (Cd 6 [A-->T]), six beta-thalassaemic alleles and 17 G6PD-deficient alleles, selected from a group of carriers or affected subjects. RESULTS: Allele frequencies were 3% for haemoglobin S, 1% for beta-thalassaemia trait and 9.5% for G6PD deficiency. Molecular analysis had revealed that the African alleles are predominant, being present in almost all the subjects studied. Mediterranean alleles were found for all the beta-thalassaemia mutations and for three G6PD chromosomes out of 17. CONCLUSION: These data are consistent with the mixed Arab and African origin of the population of the Comoro Islands, and are of clinical interest in prenatal and newborn screening plans.
UI - 11905664
AU - Muller H; Eeles RA; Wildsmith T; McGleenan T; Friedman S
TI - Genetic testing for cancer predisposition--an ongoing debate.
SO - Lancet Oncol 2000 Oct;1():118-24
AD - Division of Medical Genetics UKBB, Department of Clinical-Biological Sciences, Basel, Switzerland. Hansjakob.Mueller@unibas.ch
UI - 12026741
AU - Burgess MM; d'Agincourt-Canning L
TI - Genetic testing for hereditary disease: attending to relational responsibility.
SO - J Clin Ethics 2001 Winter;12(4):361-72
AD - Centre for Applied Ethics, University of British Columbia, Vancouver, British Columbia. firstname.lastname@example.org
UI - 11937005
AU - Compston A; Sawcer S
TI - Genetic analysis of multiple sclerosis.
SO - Curr Neurol Neurosci Rep 2002 May;2(3):259-66
AD - University of Cambridge Neurology Unit, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, United Kingdom. email@example.com
The increased recurrence risk within families indicates a role for genetic factors in the etiology of multiple sclerosis. Genes may influence susceptibility to the development of multiple sclerosis and the subsequent course of the disease. To date, associations have only been demonstrated consistently with class II major histocompatibility complex (MHC) alleles. The relatively low yield from additional candidate gene studies is only modestly advanced by several whole-genome linkage analyses, and by the first in a series of planned whole-genome linkage disequilibrium screens for allelic associations. The aims of linkage and association are to narrow the search for chromosomal regions encoding genes for multiple sclerosis and, with information from the human gene project, suggest new positional candidates. In time, it is expected that these genes will include some that confer susceptibility to the general process of autoimmunity, others that are specific for multiple sclerosis in all populations, some that act only in defined ethic groups, and those that determine particular phenotypes or shape the clinical course. These genetic analyses are predicated on the assumption that multiple sclerosis is one disease; a major part of future studies will be to resolve the question of disease heterogeneity in multiple sclerosis. When eventually in place, the potential of this genetic knowledge for improved understanding of the pathogenesis of multiple sclerosis and designing novel treatments is considerable.
UI - 11858318
AU - Burrer CV; Bauer SM
TI - Insights into genetic testing for colon cancer: the nurse practitioner role.
SO - Clin Excell Nurse Pract 2000 Nov;4(6):349-55
AD - Department of Nursing, Worcester State College, Massachusetts 01602-2597, USA. firstname.lastname@example.org
As new genetic discoveries continue to gain public awareness, patients will increasingly call on their nurse practitioners (NPs) to discuss their inherited susceptibility to disease. Genetic testing for colon cancer can presently identify gene mutations for 2 inherited forms of this disease, familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, accounting for approximately 6% of the cases. By identifying patients at high risk for colon cancer, NPs can discuss the benefits of early detection through screening procedures while helping patients gain insight into the meaning and impact genetic testing can have on their lives. This article discusses the basic genetics involved and screening recommendations for those with a hereditary disposition to colon cancer. Benefits, risks, and limitations are also considered, along with the importance of the NP in educating and supporting individuals in their decision making about genetic testing for colon cancer.
UI - 12044052
AU - Munzarova M
TI - Genetic susceptibility to malignant diseases--ethical issues. Minireview.
SO - Neoplasma 2002;49(1):1-4
AD - Institute of Medical Ethics Medical Faculty, Masaryk University, Brno, Czech Republic. email@example.com
Ethical problems connected with genetic testing with the intention of the measurement of the susceptibility or predisposition to malignant tumors are presented (respect for autonomy, beneficence, nonmaleficence, confidentiality, privacy, veracity and truth-telling, informed consent, right to know, right not to know, informational self-determination, etc.). Various aspects dealing with ethics of screening and research projects involving human subjects are discussed as well.
UI - 11929791
AU - Taub JW; Konrad MA; Ge Y; Naber JM; Scott JS; Matherly LH; Ravindranath
TI - Y High frequency of leukemic clones in newborn screening blood samples of children with B-precursor acute lymphoblastic leukemia.
SO - Blood 2002 Apr 15;99(8):2992-6
AD - Division of Pediatric Hematology/Oncology, Children's Hospital of Michigan, Detroit, Michigan 48201, USA. firstname.lastname@example.org
The detection of leukemia cells on newborn genetic screening cards ("Guthrie cards") of a small group of patients and several sets of identical twins developing acute lymphoblastic leukemia (ALL) with identical phenotypic and chromosomal markers has provided evidence that childhood ALL cases may arise in utero. We conducted a retrospective study of a randomly selected group of childhood B-precursor ALL patients to determine the frequency of the presence of "leukemic" clones prenatally in ALL cases by testing newborn screening cards. The 17 ALL patients analyzed had a median age of 46 months (range, 18 months to 13 years) and had median presenting white blood cell (WBC) counts of 10 950/microL (range, 2900-70 300/microL) at diagnosis. A clonal rearrangement of the immunoglobulin heavy chain (IgH) gene was identified in diagnostic lymphoblasts and sequenced and patient-specific primers were used to amplify DNA from blood samples on the patient's newborn screening cards. Twelve of the 17 (71%) analyzed newborn cards had detectable IgH rearrangements amplified by seminested polymerase chain reaction. DNA sequencing confirmed that the IgH rearrangements detected matched the IgH sequences identified from diagnostic leukemia cells, indicating the presence of a "leukemic" clone at birth. There were no differences in age or presenting WBC counts between the cases with or without positive newborn screening cards. All 6 patients with hyperdiploid ALL had detectable "leukemic" clones on their cards. The results of our study support the notion that a high proportion of childhood B-precursor ALL cases arise in utero, although postnatal events are also important factors in leukemogenesis.
UI - 11949635
AU - Hangaishi A; Ogawa S; Qiao Y; Wang L; Hosoya N; Yuji K; Imai Y; Takeuchi
TI - K; Miyawaki S; Hirai H Mutations of Chk2 in primary hematopoietic neoplasms.
SO - Blood 2002 Apr 15;99(8):3075-7
UI - 12013534
AU - Foulkes WD; Rosenblatt J; Chappuis PO
TI - The contribution of inherited factors to the clinicopathological features and behavior of breast cancer.
SO - J Mammary Gland Biol Neoplasia 2001 Oct;6(4):453-65
AD - Department of Oncology, McGill University, Montreal, Quebec, Canada. email@example.com
This review is focused on genetic factors that may influence the development and/or appearance of breast cancer metastases. Over the last decade there have been significant advances in the understanding of genetic predisposition to breast cancer. The first breast cancer predisposing gene to be identified was TP53, and this was followed over the next 5 years by two more genes, BRCA1 and BRCA2, which from a population perspective are much more important than TP53. Other rarer genes have subsequently been identified, but the role of more common, less penetrant genes in breast cancer susceptibility remains unknown. Recent work has shown that breast cancers occurring in women carrying germ-line BRCA1 mutations tend to have clinicopathological features that are usually associated with a poor prognosis, such as high grade, estrogen receptor negative status and somatic TP53 mutations. On the other hand, they are usually ERBB2 negative. Whether or not such tumors are more or less likely to metastasize, and hence be associated with a poor outcome, is currently uncertain and has been the subject of much debate. Here, we outline some of the clinicopathological features of hereditary breast cancer, discuss the prognostic studies that have been performed, and introduce some possible new research directions.
UI - 11902192
AU - Brady T
TI - The ethical implications of the Human Genome Project for the workplace.
SO - Int J Appl Philos 1995 Summer;10(1):47-56
AD - Business Adminstration Division Head, Holy Family College, Philadelphia, PA, USA.
UI - 11914044
AU - Njajou OT; Vaessen N; Oostra B; Heutink P; Van Duijn CM
TI - The hemochromatosis N144H mutation of SLC11A3 gene in patients with type 2 diabetes.
SO - Mol Genet Metab 2002 Mar;75(3):290-1
UI - 11987021
AU - Jungck M; Sauerbruch T
TI - [Cost-effectiveness of screening in familial adenomatous polyposis]
SO - Dtsch Med Wochenschr 2002 May 3;127(18):980-1
UI - 10785486
AU - Rose PG; Shrigley R; Wiesner GL
TI - Germline BRCA2 mutation in a patient with fallopian tube carcinoma: a case report.
SO - Gynecol Oncol 2000 May;77(2):319-20
AD - Division of Gynecologic Oncology, Center for Human Genetics, Department of Genetics, University Hospitals of Cleveland, Western Reserve University, Ohio 44106, USA.
OBJECTIVES: Fallopian tube carcinoma is similar to ovarian and peritoneal carcinoma with respect to histology, response to chemotherapy, and prognosis. BRCA germline mutations have been commonly reported in ovarian and peritoneal carcinoma but rarely in other gynecologic cancers. METHODS: A patient with fallopian tube carcinoma and a family history of ovarian carcinoma underwent genetic counseling and BRCA testing as did her daughter. RESULTS: The patient and her daughter were found to have a germline BRCA2 mutation. CONCLUSION: Like a family history of ovarian or peritoneal carcinoma, the occurrence of fallopian tube cancer should alert the clinician to the possibility of an abnormality in the breast cancer susceptibility 1 or 2 genes. Copyright 2000 Academic Press.
UI - 11987156
AU - Cormier L; Valeri A; Azzouzi R; Fournier G; Cussenot O; Berthon P;
TI - Guillemin F; Mangin P Worry and attitude of men in at-risk families for prostate cancer about genetic susceptibility and genetic testing.
SO - Prostate 2002 Jun 1;51(4):276-85
AD - Department of Urology, CHU Nancy-Brabois, Vandoeuvre-les-Nancy, France. firstname.lastname@example.org
BACKGROUND: The aim of this study was to evaluate worry about genetic susceptibility and the attitude of men with family history of prostate cancer (CaP) toward genetic testing. METHODS: Three hundred seventy-five eligible first-degree relatives (FDR) of men with CaP, were asked to participate in a screening and to fill out a survey covering the worry about genetic susceptibility and interest in genetic testing. RESULTS: Of the 375 candidates contacted, 277 completed the survey, and had undergone PSA measurement. Sixty-four percent worried a little or not at all about inherited predisposition to CaP, while the remainder worried a lot or extremely. The candidates who worried a lot or extremely were men with high levels of durable anxiety disposition (STAI trait), who had undergone a previous screening procedure and men with sons. Ninety-eight percent of men expressed their interest in undergoing genetic testing. The most motivated candidates to have the test done were men with several relatives with CaP. CONCLUSIONS: The level of worry about genetic susceptibility was low and there was a concrete interest in genetic testing in FDR of men with CaP. This interest increased with the number of CaP in the family. Copyright 2002 Wiley-Liss, Inc.
UI - 8031531
AU - Kotze MJ; Langenhoven E; Theart L; Marx MP; Oosthuizen CJ
TI - Report on a molecular diagnostic service for familial hypercholesterolemia in Afrikaners.
SO - Genet Couns 1994;5(1):15-21
AD - Department of Human Genetics, Faculty of Medicine, University of Stellenbosch, Tygerberg, South Africa.
The development of DNA-based methods for the direct detection of specific low density lipoprotein receptor (LDLR) gene mutations enabled us to establish a molecular diagnostic service for familial hypercholesterolemia (FH). This specialised service is of particular relevance and can be applied in the Afrikaner population of South Africa, where a founder gene effect increased the prevalence of FH to about 5-10 times greater than that found in most other population groups. Three point mutations in the LDLR gene were shown to account for approximately 90% of all Afrikaner FH cases. We report on the results obtained in 354 Afrikaner hyperlipidemics, from 274 unrelated families, referred for mutation screening-during the four-year period following the elucidation of the molecular basis of FH in this South African population group. By screening for the three founder-related LDLR gene mutations, approximately 50% of referrals were diagnosed as having FH. Presymptomatic diagnosis of FH by DNA analysis overcame the difficulties involved in the clinical diagnosis of some heterozygous cases. We could offer appropriate genetic counselling to FH patients, in addition to optimal clinical management by clinicians who referred the patients. Genetic testing has made early diagnosis of FH, including prenatal diagnosis, a reality.
UI - 12039933
AU - Berry DA; Iversen ES Jr; Gudbjartsson DF; Hiller EH; Garber JE; Peshkin
TI - BN; Lerman C; Watson P; Lynch HT; Hilsenbeck SG; Rubinstein WS; Hughes KS; Parmigiani G BRCAPRO validation, sensitivity of genetic testing of BRCA1/BRCA2, and prevalence of other breast cancer susceptibility genes.
SO - J Clin Oncol 2002 Jun 1;20(11):2701-12
AD - Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA. email@example.com
PURPOSE: To compare genetic test results for deleterious mutations of BRCA1 and BRCA2 with estimated probabilities of carrying such mutations; to assess sensitivity of genetic testing; and to assess the relevance of other susceptibility genes in familial breast and ovarian cancer. PATIENTS AND METHODS: Data analyzed were from six high-risk genetic counseling clinics and concern individuals from families for which at least one member was tested for mutations at BRCA1 and BRCA2. Predictions of genetic predisposition to breast and ovarian cancer for 301 individuals were made using BRCAPRO, a statistical model and software using Mendelian genetics and Bayesian updating. Model predictions were compared with the results of genetic testing. RESULTS: Among the test individuals, 126 were Ashkenazi Jewish, three were male subjects, 243 had breast cancer, 49 had ovarian cancer, 34 were unaffected, and 139 tested positive for BRCA1 mutations and 29 for BRCA2 mutations. BRCAPRO performed well: for the 150 probands with the smallest BRCAPRO carrier probabilities (average, 29.0%), the proportion testing positive was 32.7%; for the 151 probands with the largest carrier probabilities (average, 95.2%), 78.8% tested positive. Genetic testing sensitivity was estimated to be at least 85%, with false-negatives including mutations of susceptibility genes heretofore unknown. CONCLUSION: BRCAPRO is an accurate counseling tool for determining the probability of carrying mutations of BRCA1 and BRCA2. Genetic testing for BRCA1 and BRCA2 is highly sensitive, missing an estimated 15% of mutations. In the populations studied, breast cancer susceptibility genes other than BRCA1 and BRCA2 either do not exist, are rare, or are associated with low disease penetrance.
UI - 11157780
AU - Tlsty TD
TI - Searching for targets: the power of somatic cell genetics.
SO - Genome Res 2001 Feb;11(2):187-8
AD - Department of Pathology, UCSF Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California 94143-0506, USA. firstname.lastname@example.org
UI - 11979598
AU - Yesley MS
TI - Protecting genetic difference.
SO - Berkeley Technol Law J 1998 Spring;13(2):653-65
UI - 12041296
AU - Florida. District Court of Appeal, First District
TI - Pate v. Threlkel.
SO - Wests South Report 1994 Aug 1 (date of decision);640():183-6
UI - 12041297
AU - Florida. Supreme Court
TI - Pate v. Threlkel.
SO - Wests South Report 1995 Jul 20 (date of decision);661():278-82
UI - 11878343
AU - Frontali M; Jacopini AG
TI - Genetic counselling: evolution or involution?
SO - Community Genet 2000 May;3(4):175-8
AD - Instituto di Medicina Sperimentale CNR, Via Fosso del Cavaliere, I-00044 Frascati, Rome (Italy). Marina.Frontali@ims.rm.cnr.it
The need for genetic counselling derives from the peculiarities of genetic information, as compared to other biomedical tests, with particular reference to (a) its predictive character; (b) the existing gap between the ability to diagnose and to treat an inherited disorder, and (c) the psychological, social and ethical problems that genetic testing can raise. Counselling is traditionally performed by healthcare professionals, specifically trained to help individuals to develop ways of dealing with genetic information and gain a better understanding of the problems related with it. The growing number of genetic tests (for rare Mendelian as well as for common disorders), the development of easier and cheaper molecular techniques, the increasing tendency of physicians to have recourse to genetic tests, by-passing alternative diagnostic procedures, are all factors that contribute to the vast increase in the demand for genetic tests, a demand which is significantly out of step with the available numbers of trained counsellors. This paper discusses possible solutions, including the institution of committees with regulatory powers on genetic testing, the promotion of studies on models of genetic services, on programmes to monitor the services currently offered by test providers, and the expansion of training programmes and of employment opportunities for genetic counsellors.
UI - 11938683
AU - Spinelli C; Puccini M; Bertocchini A; Lima M; Pacini F; Miccoli P
TI - [Prophylactic total thyroidectomy in children and adolescents with genetic mutations in the RET-protooncogene.]
SO - Pediatr Med Chir 2002 Jan-Feb;24(1):53-7
AD - Dipartimento di Chirurgica Generale, Universita di Pisa, Via Roma, 67, Pisa.
Medullary thyroid cancer (C.M.T.) can be a sporadic form generally in adults or a heredofamilial form where the first symptom appears in pediatric and adolescent age. The hereditary form can be isolated or associated with others endocrine neoplasias of type 2: MEN2a (with or without cutaneous lichen amyloidosis) and MEN2b. The responsible gene of the transmission has been identified in proto-oncogene RET localized on chromosome 10. Point form mutations of this proto-oncogene have been found on exons 10 and 11 in MEN2a and on 16 in MEN2b. In our study on 64 subjects, who belong 11 familiar groups, affected by MEN2a, MEN2b and familiar C.M.T., underwent a genetic research to look for point form mutations of proto-oncogene RET with PCR followed by the analysis of restriction. A genetic mutation has been revealed in 25 subjects: 18 were already known affected by MEN2 and so surgical treated and 7 seemed healthy (mean age 17.4 years, range 10-25). These 7 patients has been undergone clinical research and surgical treatment: a total thyroidectomy associated a lymphectomy of the central compartment. In all cases the histological exam showed C.M.T. moreover a patient had metastasis in lymph nodes of the central compartment. Another had hyperparathyroidism and pheochromocytoma treated with total thyroidectomy, parathyroidectomy and bilateral laparoscopic adrenalectomy. The identification in a very early age of carrier subjects of hill's gene inside an affected family, permits the execution of a prophylactic total thyroidectomy to prevent the C.M.T.. The penetrance of this neoplasia in hereditary form is 100%.
UI - 11959426
AU - Zhang B; Tan Z; Zhang C; Shi Y; Lin Z; Gu N; Feng G; He L
TI - Polymorphisms of chromogranin B gene associated with schizophrenia in Chinese Han population.
SO - Neurosci Lett 2002 May 3;323(3):229-33
AD - Bio-X Life Science Research Center, Shanghai Jiao Tong University, Shanghai 200030, PR China.
Chromogranin is a widespread family of proteins in the neurosystem, whose function is guiding the sorting and secretion of neuropeptides. Using functional and positional evidences, chromogranin B was selected as a candidate gene for schizophrenia. We systematically screened all the promoter and exon regions of the gene and detected 15 single nucleotide polymorphisms (SNPs), among which four SNPs (including two non-synonymous SNPs) were selected for association analysis. In a cohort of Chinese Han schizophrenia cases and controls, the results of both the individual SNPs and the haplotypes of SNPs were significantly positive (P<0.01). Our results confirm the role of neuropeptides in the pathogenesis of schizophrenia.
UI - 7886138
AU - Schutzer PJ
TI - Genetics and ethics.
SO - Pharos Alpha Omega Alpha Honor Med Soc 1995 Winter;58(1):26-31
UI - 11840496
AU - Coyne JC; Kruus L; Kagee A; Thompson R; Palmer S; Kruus L
TI - Benign mental health consequences of screening for mutations of BRCA1/BRCA2.
SO - Am J Med Genet 2002 Feb 1;107(4):346-9
UI - 12048272
AU - Euhus DM; Smith KC; Robinson L; Stucky A; Olopade OI; Cummings S; Garber
TI - JE; Chittenden A; Mills GB; Rieger P; Esserman L; Crawford B; Hughes KS; Roche CA; Ganz PA; Seldon J; Fabian CJ; Klemp J; Tomlinson G Pretest prediction of BRCA1 or BRCA2 mutation by risk counselors and the computer model BRCAPRO.
SO - J Natl Cancer Inst 2002 Jun 5;94(11):844-51
AD - The University of Texas Southwestern Medical Center at Dallas, 75390-9155, USA. david.euhus@UTSouthwestern.edu
BACKGROUND: Because BRCA gene mutation testing is costly, occasionally uninformative, and frequently associated with ethical and legal issues, careful patient selection is required prior to testing. Estimation of BRCA gene mutation probability is an important component of pretest counseling, but the accuracy of these estimates is currently unknown. We measured the performance of eight cancer risk counselors and of a computer model, BRCAPRO, at identifying families likely to carry a BRCA gene mutation. METHODS: Eight cancer risk counselors and the computer model BRCAPRO estimated BRCA gene mutation probabilities for 148 pedigrees selected from an initial sample of 272 pedigrees. The final sample was limited to pedigrees with a proband affected by breast or ovarian cancer and BRCA1 and BRCA2 gene sequencing results unequivocally reported as negative or positive for a deleterious mutation. Sensitivity, specificity, negative predictive value, positive predictive value, and areas under receiver operator characteristics (ROC) curves were calculated for each risk counselor and for BRCAPRO. All statistical tests were two sided. RESULTS: Using a greater-than-10% BRCA gene mutation probability threshold, the median sensitivity for identifying mutation carriers was 94% (range = 81% to 98%) for the eight risk counselors and 92% (range = 91% to 92%) for BRCAPRO. Median specificity at this threshold was 16% (range = 6% to 34%) for the risk counselors and 32% (range = 30% to 34%) for BRCAPRO (P =.04). Median area under the ROC curves was 0.671 for the risk counselors (range = 0.620 to 0.717) and 0.712 (range = 0.706 to 0.720) for BRCAPRO (P =.04). There was a slight, but not statistically significant, improvement in all counselor performance measures when BRCAPRO-assigned gene mutation probability information was included with the pedigrees. CONCLUSIONS: Sensitivity for identifying BRCA gene mutation carriers is similar for experienced risk counselors and the computer model BRCAPRO. Because the computer model consistently demonstrated superior specificity, overall discrimination between BRCA gene mutation carriers and BRCA gene mutation noncarriers was slightly better for BRCAPRO.
UI - 11968082
AU - Pagon RA; Tarczy-Hornoch P; Baskin PK; Edwards JE; Covington ML;
TI - Espeseth M; Beahler C; Bird TD; Popovich B; Nesbitt C; Dolan C; Marymee K; Hanson NB; Neufeld-Kaiser W; Grohs GM; Kicklighter T; Abair C; Malmin A; Barclay M; Palepu RD GeneTests-GeneClinics: genetic testing information for a growing audience.
SO - Hum Mutat 2002 May;19(5):501-9
AD - University of Washington, Seattle, Washington, USA.
The development and usage of two companion NIH-funded genetic testing information databases, GeneTests (www.genetests.org) and GeneClinics (www.geneclinics.org), now merged into one web site, reflect the steadily increasing use of genetic testing and the expanding audience for genetic testing information. Established in 1993 as Helix, a genetics laboratory directory of approximately 110 listings, GeneTests has grown into a database of over 900 tests for inherited diseases, a directory of over 500 international laboratories, a directory of over 1,000 U.S. and international genetics clinics, and a resource for educational/teaching materials and reports of summary genetic test data. GeneClinics, founded in 1997 as an expert-authored, peer-reviewed, disease-specific knowledge base relating genetic testing to patient care, has grown steadily, now containing over 130 expert-authored, peer-reviewed full-text entries relating genetic testing information to diagnosis, management, and genetic counseling of specific inherited diseases. In spring 2001 the two databases were merged and in October 2001 the two web sites were merged for the purpose of seamless navigation into the GeneTests-GeneClinics site (www.genetests.org or www.geneclinics.org); the GeneClinics knowledge base was renamed "GeneReviews" to avoid confusion with the U.S. and international clinic directories. As genetic testing has moved steadily out of research venues and into routine medical practice, the user audience for these databases has become international and expansive and includes healthcare providers, patients, educators, policy makers, and the media. The use of these combined resources has grown to approximately 3,200 visits/day. Copyright 2002 Wiley-Liss, Inc.
UI - 11968083
AU - Oliveira C; Bordin MC; Grehan N; Huntsman D; Suriano G; Machado JC;
TI - Kiviluoto T; Aaltonen L; Jackson CE; Seruca R; Caldas C Screening E-cadherin in gastric cancer families reveals germline mutations only in hereditary diffuse gastric cancer kindred.
SO - Hum Mutat 2002 May;19(5):510-7
AD - Cancer Genomics Program, Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Addenbrooke's Hospital, Cambridge, UK.
The International Gastric Cancer Linkage Consortium (IGCLC) predicted that up to 25% of families fulfilling the criteria for hereditary diffuse gastric cancer (HDGC) would harbor CDH1 germline mutations. This was based on observations from the low number of diffuse gastric cancer families described at the time, and its validation would require analysis of larger numbers. Here we report the results of germline CDH1 mutation screening in 39 kindred with familial aggregation of gastric cancer, a subset of which fulfills the criteria defined by the IGCLC for HDGC. CDH1 germline mutations were detected in four of 11 (36.4%) HDGC families. No mutations were identified in 63.6% of HDGC families or in kindred with familial aggregation of gastric cancer not fulfilling criteria for HDGC. These results add support to the evidence that only HDGC families harbor germline mutations in CDH1 and that genes other than CDH1 remain to be identified. Copyright 2002 Wiley-Liss, Inc.
UI - 12007222
AU - Herzog JS; Jancis EM; Liao S; Somlo G; Weitzel JN
TI - Restriction endonuclease fingerprinting enhanced conformation sensitive gel electrophoresis (REF-CSGE) in the analysis of BRCA1 exon 11 mutations in a high-risk breast cancer cohort.
SO - Hum Mutat 2002 Jun;19(6):656-63
AD - Department of Clinical Cancer Genetics, Beckman Research Institute and City of Hope (COH) Comprehensive Cancer Center, Duarte, California, USA.
Efficient genetic analysis of large exonic regions containing heterozygous mutations and common polymorphisms can be difficult. We have analyzed 30 patients for inherited susceptibility mutations (ISM) within exon 11 of the BRCA1 gene as part of an ongoing genetic epidemiological study of high-risk breast cancer (HRBC). A novel combination of restriction endonuclease fingerprinting (REF) and conformation sensitive gel electrophoresis (CSGE) was developed for rapid and efficient screening of mutations. This method (REF-CSGE) was compared side-by-side with standard CSGE and evaluated for both efficiency and sensitivity of detection. REF-CSGE detected 100% of the alterations found by CSGE. However, one variant was only detectable by REF-CSGE. All samples with variant bands were sequenced to confirm the nature of the alteration. In total, two small deletions (frameshifts) and 62 point mutations (60 known polymorphisms and two variants of unknown significance) were found in our cohort. The majority of the exon 11 polymorphisms detected are inherited as a linked haplotype. Point mutations that comprise these haplotypes could be simultaneously detected on a single gel by REF-CSGE, thereby decreasing the number of sequencing reactions necessary to elucidate heteroduplex patterns seen on CSGE gels. An analysis of the overall efficiency of both techniques revealed that REF-CSGE required 67% fewer confirmatory sequencing reactions, resulting in savings in both reagents and technician time. Copyright 2002 Wiley-Liss, Inc.
UI - 12007223
AU - Gavert N; Yaron Y; Naiman T; Bercovich D; Rozen P; Shomrat R; Legum C;
TI - Orr-Urtreger A Molecular analysis of the APC gene in 71 Israeli families: 17 novel mutations.
SO - Hum Mutat 2002 Jun;19(6):664
AD - Department of Surgery B, Tel Aviv Sourasky Medical Center, Israel.
Familial adenomatous polyposis (FAP) is caused by germline mutations in the APC gene. This study included 71 Israeli families referred for molecular analysis of the APC gene. Analysis was performed by the protein truncation test (PTT) of exon 15, and if negative, by direct sequencing of exon 1 to 14. Mutations were found in 36 (50.7%) probands. Mutation detection rates depended on the pattern of referral, such that among the 40 probands referred from the Service for Hereditary Cancer the mutation detection rate was 70%, whereas among the 31 probands referred by other gastroenterologists detection rate was significantly lower (25.8%). Of the 36 mutations detected, 21 were within exon 15, 13 within exons 1 to 14 and 2 were newly-described splicing mutations in introns 9 and 14. A relatively high proportion of the mutations was detected in exon 9 (6/36), five of them newly described. Altogether, we describe here 17 new mutations. Within the two major ethnic groups in Israel, patients of Ashkenazi and non-Ashkenazi origin, there was no significant differences in the mutation detection rate or the distribution of mutations within the APC gene. No founder mutation was detected in any of these populations. Our data confirm that higher detection rates may be expected in patients referred by clinical services specializing in hereditary colon cancer. These results further underscore the importance of complete analysis of all exons and exon/intron boundaries, in order to achieve maximal detection rate in patients suspected of FAP. Copyright 2002 Wiley-Liss, Inc.
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