{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T20:40:16Z","timestamp":1768336816562,"version":"3.49.0"},"reference-count":51,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5338","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1997,10,24]]},"abstract":"<jats:p>As increasing numbers of genes are identified and associated with human diseases, researchers are considering how to bring their discoveries from the research bench to the clinic. Holtzman, Murphy, Watson, and Barr, who were part of a Task Force on Genetic Testing sponsored by the National Institutes of Health and U.S. Department of Energy, discuss policies for regulating the development of genetic tests so that the full potential of gene discovery to help the general population can be realized.<\/jats:p>","DOI":"10.1126\/science.278.5338.602","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:37:56Z","timestamp":1027762676000},"page":"602-605","source":"Crossref","is-referenced-by-count":57,"title":["Predictive Genetic Testing: From Basic Research to Clinical Practice"],"prefix":"10.1126","volume":"278","author":[{"given":"Neil A.","family":"Holtzman","sequence":"first","affiliation":[{"name":"N. A. Holtzman is with the Genetics and Public Policy Studies, Johns Hopkins Medical Institutions, 550 North Broadway, Suite 511, Baltimore, MD 21205, USA. P. D. Murphy is in the Department of Obstetrics and Gynecology, Albany Medical Center, Albany, NY 12208, USA. M. S. Watson is in the Departments of Pediatrics and Genetics, Washington University School of Medicine, St. Louis Children's Hospital, One Children's Place, St. Louis, MO 63110, USA. P. A. Barr is with Barr, Sternberg, and Moss, PC, 507..."}]},{"given":"Patricia D.","family":"Murphy","sequence":"additional","affiliation":[{"name":"N. A. Holtzman is with the Genetics and Public Policy Studies, Johns Hopkins Medical Institutions, 550 North Broadway, Suite 511, Baltimore, MD 21205, USA. P. D. Murphy is in the Department of Obstetrics and Gynecology, Albany Medical Center, Albany, NY 12208, USA. M. S. Watson is in the Departments of Pediatrics and Genetics, Washington University School of Medicine, St. Louis Children's Hospital, One Children's Place, St. Louis, MO 63110, USA. P. A. Barr is with Barr, Sternberg, and Moss, PC, 507..."}]},{"given":"Michael S.","family":"Watson","sequence":"additional","affiliation":[{"name":"N. A. Holtzman is with the Genetics and Public Policy Studies, Johns Hopkins Medical Institutions, 550 North Broadway, Suite 511, Baltimore, MD 21205, USA. P. D. Murphy is in the Department of Obstetrics and Gynecology, Albany Medical Center, Albany, NY 12208, USA. M. S. Watson is in the Departments of Pediatrics and Genetics, Washington University School of Medicine, St. Louis Children's Hospital, One Children's Place, St. Louis, MO 63110, USA. P. A. Barr is with Barr, Sternberg, and Moss, PC, 507..."}]},{"given":"Patricia A.","family":"Barr","sequence":"additional","affiliation":[{"name":"N. A. Holtzman is with the Genetics and Public Policy Studies, Johns Hopkins Medical Institutions, 550 North Broadway, Suite 511, Baltimore, MD 21205, USA. P. D. Murphy is in the Department of Obstetrics and Gynecology, Albany Medical Center, Albany, NY 12208, USA. M. S. Watson is in the Departments of Pediatrics and Genetics, Washington University School of Medicine, St. Louis Children's Hospital, One Children's Place, St. Louis, MO 63110, USA. P. A. Barr is with Barr, Sternberg, and Moss, PC, 507..."}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","unstructured":"N. A. Holtzman Account. Res. 5 95 (1996). Headlines and news stories sometimes raise expectations of the clinical applications of new discoveries that cannot be fulfilled without additional study. See for example \u201cRare breast cancer link is tied  to European-Jewish ancestry; discovery said to promise community screening test \u201d Los Angeles Times (news service) Baltimore Sun 29 September 1995 p. 3A; \u201cGene causing colon cancer found; discovery at Hopkins expected to save thousands of lives \u201d Baltimore Sun 6 May 1993 p. 1."},{"key":"e_1_3_2_3_2","unstructured":"Public Law 100-578 Clinical Laboratory Improvement Amendments of 1988 42 USC 263a et seq."},{"key":"e_1_3_2_4_2","unstructured":"Although the FDA has stated that genetic tests fall under its regulatory authority as \u201cmedical devices \u201d the agency has chosen only to regulate clinical laboratory tests marketed as kits or other tangible products not those marketed as services."},{"key":"e_1_3_2_5_2","unstructured":"Sensitivity is the probability that people who have or will develop a disease can be detected by the test. PVP is the probability that a person with a positive test result will develop the disease the test is designed to detect. Often a test can be used for other purposes (off-label use). For example in addition to being used predictively to detect those at risk of the Li-Fraumeni syndrome a test for p53 mutations can be used to diagnose the syndrome in individuals with cancer and a suggestive family history or to stage a tumor by detecting somatic p53 mutations. The requirements for sensitivity and PVP could differ depending on the intended use."},{"key":"e_1_3_2_6_2","unstructured":"Analytical validity is the ability of the test to correctly identify the analyte it is designed to detect. In the CLIA certification process a clinical laboratory must demonstrate the tests' analytical validity to outside surveyors who inspect laboratories approximately every 2 years."},{"key":"e_1_3_2_7_2","unstructured":"Task Force on Genetic Testing Promoting Safe and Effective Genetic Testing in the United States Final Report N. A. Holtzman and M. S. Watson Eds. (National Institutes of Health Bethesda MD 1997). Also available at ."},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8091226"},{"key":"e_1_3_2_9_2","unstructured":"Over 150 BRCA1 ISMs have been identified but they do not account for all patients with linkage to chromosome 17q21 [F. J. Couch B. L. Weber the Breast Cancer Information Core Hum. Mutat. 8 8 (1996)]. Locus heterogeneity also occurs further reducing sensitivity. At least two genes BRCA1 and BRCA2 increase susceptibility to breast cancer ["},{"key":"e_1_3_2_9_3","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1056\/NEJM199705153362009","volume":"336","author":"Healy B.","year":"1997","unstructured":"Healy B., N. Engl. J. Med. 336, 1448 (1997);","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_2_9_4","unstructured":"] and five to colon cancer ["},{"key":"e_1_3_2_9_5","doi-asserted-by":"publisher","DOI":"10.1038\/ng0997-79"},{"key":"e_1_3_2_9_6","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1056\/NEJM199503303321306","volume":"332","author":"Toribara N. W.","year":"1995","unstructured":"Toribara N. W., Sleisenger M. H., N. Engl. J. Med. 332, 861 (1995)].","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_2_10_2","unstructured":"The first report of linkage of familial breast cancer to chromosome 17q21 ["},{"key":"e_1_3_2_10_3","doi-asserted-by":"publisher","DOI":"10.1126\/science.2270482"},{"key":"e_1_3_2_10_4","unstructured":"] involved 23 extended families with an average of 6.3 cases per family. The study describing the risk of breast and ovarian cancer in BRCA1 mutation carriers was based on families in which a combination of at least four cases of ovarian cancer at any age or breast cancer before age 60 were present [D. F. Easton D. Ford D. T. Bishop the Breast Cancer Linkage Consortium Am. J. Hum. Genet. 56 265 (1995)]."},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1093\/jnci\/87.15.1126","volume":"87","author":"Schatzkin A.","year":"1995","unstructured":"Schatzkin A., Goldstein A., Freedman L. S., J. Natl. Cancer Inst. 87, 1126 (1995);","journal-title":"J. Natl. Cancer Inst."},{"key":"e_1_3_2_11_3","unstructured":". Struewing et al. recently found that the risk of developing breast cancer among women drawn from the general population of Ashkenazi Jews before age 70 years was 56% ["},{"key":"e_1_3_2_11_4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199705153362001"},{"key":"e_1_3_2_11_5","unstructured":"] which is lower than the 85% risk of breast cancer in families with multiple affected members used in the research studies ["},{"key":"e_1_3_2_11_6","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/ng0797-210","volume":"16","author":"Easton D.","year":"1997","unstructured":"Easton D., Nature Genet. 16, 210 (1997);","journal-title":"Nature Genet."},{"key":"e_1_3_2_11_7","unstructured":"]. The association of late-onset AD in people with the apoE4 polymorphism is greater in families with multiple affected members than in sporadic cases ["},{"key":"e_1_3_2_11_8","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1001\/archneur.1995.00540350068018","volume":"52","author":"Seshadri S.","year":"1995","unstructured":"Seshadri S., Drachman D. A., Lippa C. F., Arch. Neurol. 52, 1074 (1995);","journal-title":"Arch. Neurol."},{"key":"e_1_3_2_11_9","doi-asserted-by":"crossref","unstructured":"; National Institute on Aging Lancet 347 1091 (1996)].","DOI":"10.1016\/S0140-6736(96)90284-6"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1056\/NEJM198606193142501","volume":"314","author":"Gaston M. H.","year":"1986","unstructured":"Gaston M. H., et al., N. Engl. J. Med. 314, 1593 (1986);","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_2_12_3","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1542\/peds.81.6.749","volume":"81","author":"Vichinsky E.","year":"1988","unstructured":"Vichinsky E., Hurst D., Earles A., Kleman K., Lubin B., Pediatrics 81, 749 (1988);","journal-title":"Pediatrics"},{"key":"e_1_3_2_12_4","doi-asserted-by":"crossref","unstructured":"; N. A. Holtzman R. A. Kronmal W. van Doorninck C. Azen R. Koch N. Engl. J. Med. 314 593 ( 1986).","DOI":"10.1056\/NEJM198603063141001"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/0168-9525(96)10012-3","volume":"12","author":"Pasini B.","year":"1996","unstructured":"Pasini B., Ceccherini I., Romeo G., Trends Genet. 12, 138 (1996).","journal-title":"Trends Genet."},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1002\/ajmg.1320560404","volume":"56","author":"Treacy E.","year":"1995","unstructured":"Treacy E., Childs B., Scriver C. R., Am. J. Hum. Genet. 56, 359 (1995).","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1001\/jama.1997.03540350065035","volume":"277","author":"Burke W.","year":"1997","unstructured":"Burke W., et al., J. Am. Med. Assoc. 277, 915 (1997);","journal-title":"J. Am. Med. Assoc."},{"key":"e_1_3_2_15_3","unstructured":"; W. Burke et al. ibid. p. 997."},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","unstructured":"N. A. Holtzman Adv. Oncol. 13 (no. 1) 9 (1997).","DOI":"10.1002\/(SICI)1098-2388(199701\/02)13:1<34::AID-SSU6>3.0.CO;2-5"},{"key":"e_1_3_2_17_2","first-page":"626","volume":"55","author":"Tambor E. S.","year":"1994","unstructured":"Tambor E. S., et al., Am. J. Hum. Genet. 55, 626 (1994);","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_3_2_17_3","unstructured":"; R. T. Croyle D. S. Dutson V. T. Tran Y. Sun Women's Health Res. Gender Behav. Pol. 1 329 (1995)."},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","unstructured":"N. S. Wexler FASEB J. 6 2820 (1992).","DOI":"10.1096\/fasebj.6.10.1386047"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5235.391"},{"key":"e_1_3_2_19_3","first-page":"1755","volume":"275","author":"Rothenberg K. H.","year":"1997","unstructured":"Rothenberg K. H., et al., ibid. 275, 1755 (1997);","journal-title":"ibid."},{"key":"e_1_3_2_19_4","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/oxfordjournals.epirev.a017939","volume":"19","author":"Holtzman N. A.","year":"1997","unstructured":"Holtzman N. A., Andrews L. B., Epidemiol. Rev. 19, 163 (1997).","journal-title":"Epidemiol. Rev."},{"key":"e_1_3_2_20_2","unstructured":"Until they were confident that locus heterogeneity did not exist the Huntington researchers refused to make their probes available outside of investigative protocols ["},{"key":"e_1_3_2_20_3","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/320021b0","volume":"320","author":"Gusella J. F.","year":"1986","unstructured":"Gusella J. F., Nature 320, 329 (1986);","journal-title":"Nature"},{"key":"e_1_3_2_20_4","unstructured":"; ibid. 323 118 (1986)]. In addition concern about the psychological impact of identifying people at risk of a fatal untreatable disease led to pilot programs with extensive guidelines for counseling and support for those considering predictive testing many of which have been retained as testing has become available in health care ["},{"key":"e_1_3_2_20_5","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1136\/jmg.27.1.34","volume":"27","author":"De Somviele C.","year":"1990","unstructured":"De Somviele C., et al., J. Med. Genet. 27, 34 (1990)].","journal-title":"J. Med. Genet."},{"key":"#cr-split#-e_1_3_2_21_2.1","doi-asserted-by":"crossref","unstructured":"National Institutes of Health N. Engl. J. Med. 323 70 (1990)","DOI":"10.1056\/NEJM199007053230130"},{"key":"#cr-split#-e_1_3_2_21_2.2","unstructured":"American Society of Human Genetics Am. J. Hum. Genet. 46 393 (1990)."},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/nm0696-613","volume":"2","author":"Smith O.","year":"1996","unstructured":"Smith O., Nature Med. 2, 613 (1996).","journal-title":"Nature Med."},{"key":"#cr-split#-e_1_3_2_23_2.1","doi-asserted-by":"crossref","unstructured":"American Society of Clinical Oncology J. Clin. Oncol. 14 1730 (1996)","DOI":"10.1200\/JCO.1996.14.5.1730"},{"key":"#cr-split#-e_1_3_2_23_2.2","unstructured":"American Society of Human Genetics Ad Hoc Committee Am. J. Hum. Genet. 55 1 (1994)."},{"key":"#cr-split#-e_1_3_2_24_2.1","doi-asserted-by":"crossref","unstructured":"American College of Medical Genetics and American Society of Human Genetics Working Group on ApoE and Alzheimer Disease J. Am. Med. Assoc. 274 1627 (1995)","DOI":"10.1001\/jama.274.20.1627"},{"key":"#cr-split#-e_1_3_2_24_2.2","doi-asserted-by":"crossref","unstructured":"National Institute on Aging Lancet 347 1091 (1996).","DOI":"10.1016\/S0140-6736(96)90284-6"},{"key":"e_1_3_2_25_2","unstructured":"Additional characteristics include the likelihood that a test will have low sensitivity (because of genetic heterogeneity) and low PVP (because of incomplete penetrance) and the absence of an intervention proven to be effective in those with positive test results. Tests for disorders of high prevalence for screening populations or for use selectively in ethnic groups with higher incidence or prevalence of the disorder are other characteristics that might increase the priority for review."},{"key":"e_1_3_2_26_2","unstructured":"See for example R. R. Howell et al. NIH Consensus Development Conference Statement: Genetic Testing for Cystic Fibrosis in press."},{"key":"e_1_3_2_27_2","unstructured":"Preparation of this paper was supported in part by the National Human Genome Research Institute. The views expressed in this paper are entirely those of the authors and do not necessarily represent the organizations with which they are affiliated."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.278.5338.602","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T04:43:46Z","timestamp":1705121026000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.278.5338.602"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,10,24]]},"references-count":51,"journal-issue":{"issue":"5338","published-print":{"date-parts":[[1997,10,24]]}},"alternative-id":["10.1126\/science.278.5338.602"],"URL":"https:\/\/doi.org\/10.1126\/science.278.5338.602","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,10,24]]}}}