{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:27:03Z","timestamp":1791973623115,"version":"4.4.0"},"reference-count":10,"publisher":"BMJ","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1996,11]]},"abstract":"<jats:p>We have previously described in tuberous sclerosis (TSC) hamartomas the phenomenon of loss of heterozygosity (LOH) for DNA markers in the region of both the TSC2 gene on chromosome 16p13.3 and the TSC1 gene on 9q34. We now describe the spectrum of LOH in 51 TSC hamartomas from 34 cases of TSC. DNA was extracted from leucocytes or normal paraffin embedded tissue, and from frozen paraffin embedded hamartoma tissue from the same patient. The samples were analysed for 11 markers spanning the TSC1 locus and nine markers spanning the TSC2 locus. Twenty-one of 51 hamartomas showed LOH (41%). There was significantly more LOH on 16p13.3, with 16 hamartomas showing LOH around TSC2, and five in the vicinity of TSC1. No hamartoma showed LOH for markers around both loci. All the areas of LOH on chromosome 9 were large, but the smallest region of overlap lay between the markers D9S149 and D9S114, providing independent evidence for the localisation of the TSC1 gene. These data show that LOH is a common finding in a wide range of hamartomas, affecting the same TSC locus in different lesions from the same patient but not affecting both loci. These data support the hypothesis that both the TSC genes act as tumour suppressors and that the manifestations of TSC in patients with germline TSC mutations rise from \"second hit\" somatic mutations inactivating the remaining normal copy of the TSC gene.<\/jats:p>","DOI":"10.1136\/jmg.33.11.962","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"962-964","source":"Crossref","is-referenced-by-count":130,"title":["Loss of heterozygosity in tuberous sclerosis hamartomas."],"prefix":"10.1136","volume":"33","author":[{"given":"T","family":"Sepp","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J R","family":"Yates","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A J","family":"Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1996,11,1]]},"reference":[{"key":"ref_1","first-page":"2","article-title":"Two loci for tuberous sclerosis: one on 9q34 and one on 16pl3","volume":"58","author":"Povey, S.; Burley, M.W.; Attwood, J.","year":"1994","unstructured":"Povey S, Burley MW, Attwood J, et al. Two loci for tuberous sclerosis: one on 9q34 and one on 16pl3. Ann Hum Genet 1994;58(pt 2):107-27."},{"issue":"3","key":"ref_2","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1469-1809.1994.tb01887.x","article-title":"Report and abstracts of the Third Intemational Workshop on Chromosome 9","volume":"58","author":"Povey, S.; Armour, J.; Famdon, P.","year":"1994","unstructured":"Povey S, Armour J, Famdon P, et al. Report and abstracts of the Third Intemational Workshop on Chromosome 9, Cambridge, United Kingdom, 9-11 April, 1994. Ann Hum Genet 1994;58(pt 3):177-250.","journal-title":"Ann Hum Genet"},{"key":"ref_3","first-page":"1","article-title":"The European Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterisation of the tuberous sclerosis gene on chromosome 16","volume":"75","year":"1993","unstructured":"The European Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterisation of the tuberous sclerosis gene on chromosome 16. Cell 1993;75:1-11.","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"16409","DOI":"10.1074\/jbc.270.27.16409","article-title":"Identification of tuberin, the tuberous sclerosis-2 product. Tuberin possesses specific RapIGAP activity","volume":"270","author":"Wienecke, R.; Konig, A.; DeClue, J.E.","year":"1995","unstructured":"Wienecke R, Konig A, DeClue JE. Identification of tuberin, the tuberous sclerosis-2 product. Tuberin possesses specific RapIGAP activity. JBiol Chem 1995;270:16409-14.","journal-title":"JBiol Chem"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/ng0294-193","article-title":"Loss of heterozygosity on chromosome 16pl3.3 in hamartomas from tuberous sclerosis patients","volume":"6","author":"Green, A.J.; Smith, M.; Yates, J.R.W.","year":"1994","unstructured":"Green AJ, Smith M, Yates JRW. Loss of heterozygosity on chromosome 16pl3.3 in hamartomas from tuberous sclerosis patients. Nat Genet 1994;6:193-6.","journal-title":"Nat Genet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1093\/hmg\/3.10.1833","article-title":"The tuberous sclerosis gene on chromosome 9q34 acts as a growth suppressor","volume":"3","author":"Green, A.J.; Johnson, P.H.; Yates, J.R.W.","year":"1994","unstructured":"Green AJ, Johnson PH, Yates JRW. The tuberous sclerosis gene on chromosome 9q34 acts as a growth suppressor. Hum Mol Genet 1994;3:1833-4.","journal-title":"Hum Mol Genet"},{"issue":"34","key":"ref_7","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1093\/hmg\/3.10.1829","article-title":"loss of heterozygosity in a tuberous sclerosis astrocytoma suggests a growth suppressor-like activity also for the TSC1 gene","volume":"9","author":"Carbonara, C.; Longa, L.; Grosso, E.","year":"1994","unstructured":"Carbonara C, Longa L, Grosso E, et al. 9q34 loss of heterozygosity in a tuberous sclerosis astrocytoma suggests a growth suppressor-like activity also for the TSC1 gene. Hum Mol Genet 1994;3:1829-32.","journal-title":"Hum Mol Genet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1073\/pnas.68.4.820","article-title":"Mutation and cancer: statistical study of retinoblastoma","volume":"68","author":"Knudson, A.G.J.","year":"1971","unstructured":"Knudson AGJ. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 1971;68:820-3.","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1002\/gcc.2870130411","article-title":"Loss of heterozygosity in the tuberous sclerosis (TSC2) region of chromosome band 16pl 3 occurs in sporadic as well as TSC-associated renal angiomyolipomas","volume":"13","author":"Henske, E.P.; Neumann, H.P.; Scheithauer, B.W.; Herbst, E.W.; Short, M.P.; Kwiatkowski, D.J.","year":"1995","unstructured":"Henske EP, Neumann HP, Scheithauer BW, Herbst EW, Short MP, Kwiatkowski DJ. Loss of heterozygosity in the tuberous sclerosis (TSC2) region of chromosome band 16pl 3 occurs in sporadic as well as TSC-associated renal angiomyolipomas. Genes Chrom Cancer 1995;13:295-8.","journal-title":"Genes Chrom Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/(SICI)1098-2264(199601)15:1<18::AID-GCC3>3.0.CO;2-7","article-title":"Apparent preferential loss of heterozygosity at TSC2 over TSC 1 chromosomal region in tuberous sclerosis hamartomas","volume":"15","author":"Carbonara, C.; Longa, L.; Grosso, E.","year":"1996","unstructured":"Carbonara C, Longa L, Grosso E, et al. Apparent preferential loss of heterozygosity at TSC2 over TSC 1 chromosomal region in tuberous sclerosis hamartomas. Genes Chrom Cancer 1996;15:18-25.","journal-title":"Genes Chrom Cancer"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.33.11.962","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T05:19:24Z","timestamp":1760764764000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.33.11.962"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,11]]},"references-count":10,"journal-issue":{"issue":"11","published-online":{"date-parts":[[1996,11,1]]},"published-print":{"date-parts":[[1996,11]]}},"alternative-id":["10.1136\/jmg.33.11.962"],"URL":"https:\/\/doi.org\/10.1136\/jmg.33.11.962","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,11]]}}}