{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T09:09:05Z","timestamp":1770714545354,"version":"3.49.0"},"reference-count":22,"publisher":"BMJ","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1995,11]]},"abstract":"<jats:p>Multifocal renal cell carcinomas (RCCs), together with angiomyolipomas (AMLs) and renal cysts, were identified in early adult life in two sisters with tuberous sclerosis (TSC). They were members of a multigenerational tuberous sclerosis family showing strong evidence for a mutant TSC causing gene on chromosome 9 (TSC1). Previous reports of multifocal RCC in young patients with TSC suggest that constitutional mutations at the TSC loci may predispose to RCC. In the rat a germline mutation affecting the TSC2 gene is associated with transmission of multifocal RCC as an autosomal dominant trait. However, the cases reported here are the first to suggest a similar role for the TSC1 gene in renal cell carcinogenesis.<\/jats:p>","DOI":"10.1136\/jmg.32.11.848","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:23:16Z","timestamp":1226330596000},"page":"848-850","source":"Crossref","is-referenced-by-count":45,"title":["Multifocal renal cell carcinoma in sibs from a chromosome 9 linked (TSC1) tuberous sclerosis family."],"prefix":"10.1136","volume":"32","author":[{"given":"J R","family":"Sampson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Patel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A D","family":"Mee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1995,11,1]]},"reference":[{"key":"ref_1","article-title":"Tuberous sclerosis","author":"Gomez, M.R.","year":"1988","unstructured":"Gomez MR. Tuberous sclerosis. 2nd ed. New York: Raven Press, 1988.","edition":"2nd ed"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/j.1749-6632.1991.tb37754.x","article-title":"Epidemiology of tuberous sclerosis","volume":"615","author":"Osborne, J.P.; Fryer, A.; Webb, D.","year":"1991","unstructured":"Osborne JP, Fryer A, Webb D. Epidemiology of tuberous sclerosis. Ann NYAcad Sci 1991;615:125-7.","journal-title":"Ann NYAcad Sci"},{"key":"ref_3","first-page":"659","article-title":"Evidence that the gene for tuberous sclerosis is on chromosome 9","volume":"i:","author":"Fryer, A.E.; Chalmers, A.; Connor, J.M.","year":"1987","unstructured":"Fryer AE, Chalmers A, Connor JM, et al. Evidence that the gene for tuberous sclerosis is on chromosome 9. Lancet 1987;i:659-61.","journal-title":"Lancet"},{"key":"ref_4","first-page":"27","article-title":"Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease","volume":"2","author":"Kandt, R.S.; Haines, J.L.; Smith, M.","year":"1992","unstructured":"Kandt RS, Haines JL, Smith M, et al. Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease. Nature Genet 1992;2:27-41.","journal-title":"Nature Genet"},{"key":"ref_5","first-page":"1305","article-title":"The European Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterisation of the tuberous sclerosis gene on chromosome 16","volume":"73","year":"1993","unstructured":"The European Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterisation of the tuberous sclerosis gene on chromosome 16. Cell 1993;73: 1305-15.","journal-title":"Cell"},{"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"},{"key":"ref_7","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. Nature Genet 1994;6: 193-6.","journal-title":"Nature Genet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1136\/jmg.30.3.224","article-title":"Identification of markers flanking the tuberous sclerosis locus","volume":"30","author":"Nellist, M.; Brook-Carter, P.T.; Connor, J.M.; Kwiatkowski, D.J.; Johnson, P.; Sampson, JR","year":"1993","unstructured":"Nellist M, Brook-Carter PT, Connor JM, Kwiatkowski DJ, Johnson P, Sampson JR. Identification of markers flanking the tuberous sclerosis locus on chromosome 9 (TSC1). J Med Genet 1993;30:224-7.","journal-title":"J Med Genet"},{"key":"ref_9","first-page":"11413","article-title":"Predisposition to renal cell carcinoma in the Eker rat is determined by germ-line mutation ofthe tuberous sclerosis","volume-title":"2 (TSC2) gene. Proc Natl Acad Sci USA","volume":"91","author":"Yeung, R.S.; Ziao, G.H.; Jin, W.C.; Testa, JR, Knudson; A.G.","year":"1994","unstructured":"Yeung RS, Ziao GH, Jin WC, Testa JR, Knudson AG. Predisposition to renal cell carcinoma in the Eker rat is determined by germ-line mutation ofthe tuberous sclerosis 2 (TSC2) gene. Proc Natl Acad Sci USA 1994;91:11413-16."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/ng0195-70","article-title":"Hino 0. A germline insertion in the tuberous sclerosis (TSC2) gene gives rise to the Eker rat model of dominantly inherited cancer","volume":"9","author":"Kobayashi, T.; Hirayama, Y.; Kobayashi, E.; Kubo, Y.","year":"1995","unstructured":"Kobayashi T, Hirayama Y, Kobayashi E, Kubo Y, Hino 0. A germline insertion in the tuberous sclerosis (TSC2) gene gives rise to the Eker rat model of dominantly inherited cancer. Nature Genet 1995;9:70-4.","journal-title":"Nature Genet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/BF00201608","article-title":"Refined localization of TSC 1 by combined analysis of 9q34 and 1 6p 1 3 data in 14 tuberous sclerosis families","volume":"94","author":"Janssen, B.; Sampson, J.; van der Est, M.","year":"1994","unstructured":"Janssen B, Sampson J, van der Est M, et al. Refined localization of TSC 1 by combined analysis of 9q34 and 1 6p 1 3 data in 14 tuberous sclerosis families. Hum Genet 1994; 94:437-40.","journal-title":"Hum Genet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1148\/radiology.188.1.8511293","article-title":"Hyperchoic renal tumours: anechoic rim and intratumoral cysts in ultrasound differentation of renal cell carcinoma from angiomyolipoma","volume":"188","author":"true","year":"1993","unstructured":"Yamashita Y, Ueno S, Makita 0, et al. Hyperchoic renal tumours: anechoic rim and intratumoral cysts in ultrasound differentation of renal cell carcinoma from angiomyolipoma. Radiology 1993;188:179-82.","journal-title":"Radiology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/S0022-5347(17)53053-0","article-title":"Preoperative diagnosis of coincident renal cell carcinoma and renal angiomyolipoma in non-tuberous sclerosis","volume":"128","author":"Takeyama, M.; Arima, M.; Sagawa, S.; Sonoda, T.","year":"1982","unstructured":"Takeyama M, Arima M, Sagawa S, Sonoda T. Preoperative diagnosis of coincident renal cell carcinoma and renal angiomyolipoma in non-tuberous sclerosis. J Urol 1982; 128:579-81.","journal-title":"J Urol"},{"key":"ref_14","first-page":"135","article-title":"Giant angiomyolipoma with typical arteriovenous shunting: CT and angiographic studies","volume":"73","author":"Danneels, F.; Meeus, L.; Casselman, J.W.","year":"1990","unstructured":"Danneels F, Meeus L, Casselman JW, et al. Giant angiomyolipoma with typical arteriovenous shunting: CT and angiographic studies. J Belge Radiol 1990;73: 135-7.","journal-title":"J Belge Radiol"},{"key":"ref_15","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.","year":"1971","unstructured":"Knudson AG. 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_16","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1016\/S0022-5347(17)37087-8","article-title":"Hereditary renal cell carcinoma in the Eker rat: a rodent familial cancer syndrome","volume":"148","author":"Everitt, J.I.; Goldsworthy, T.L.; Wolf, D.C.; Walker, C.L.","year":"1992","unstructured":"Everitt JI, Goldsworthy TL, Wolf DC, Walker CL. Hereditary renal cell carcinoma in the Eker rat: a rodent familial cancer syndrome. J Urol 1992;148:1932-6.","journal-title":"J Urol"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1542\/peds.80.6.898","article-title":"Renal cell carcinoma in patients with tuberous sclerosis","volume":"80","author":"Weinblatt, M.E.; Kahn, E.; Kochen, J.","year":"1987","unstructured":"Weinblatt ME, Kahn E, Kochen J. Renal cell carcinoma in patients with tuberous sclerosis. Pediatrics 1987;80: 898-903.","journal-title":"Pediatrics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/S0022-5347(17)41057-3","article-title":"Renal angiomyolipoma associated with lymph node involvement and renal cell carcinoma in patients with tuberous sclerosis","volume":"141","author":"Taylor, R.S.; Joseph, D.B.; Kohaut, E.C.; Wilson, E.R.; Bueshen, A.J.","year":"1989","unstructured":"Taylor RS, Joseph DB, Kohaut EC, Wilson ER, Bueshen AJ. Renal angiomyolipoma associated with lymph node involvement and renal cell carcinoma in patients with tuberous sclerosis. J Urol 1989;141:930-2.","journal-title":"J Urol"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"848","DOI":"10.2214\/ajr.132.5.848","article-title":"Coincident renal cell carcinoma and renal angiomyolipoma in tuberous sclerosis","volume":"132","author":"Gutierrez 0, Burgener FA, Schwartz S","year":"1979","unstructured":"Gutierrez 0, Burgener FA, Schwartz S. Coincident renal cell carcinoma and renal angiomyolipoma in tuberous sclerosis. AJR 1979;132:848-50.","journal-title":"AJR"},{"key":"ref_20","first-page":"6718","article-title":"A case ofrental cell carcinoma in tuberous sclerosis followed by basic AFP - a new carcinoembryonic protein","volume":"30","author":"Takeuchi, S.; Gotoh, S.; Tari, K.","year":"1984","unstructured":"Takeuchi S, Gotoh S, Tari K. A case ofrental cell carcinoma in tuberous sclerosis followed by basic AFP - a new carcinoembryonic protein. Hinyokika Kiyo 1984;30:6718.","journal-title":"Hinyokika Kiyo"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/0090-4295(86)90076-2","article-title":"Tuberous sclerosis with angiomyolipoma and metastasised hypernephroma","volume":"28","author":"Ahuja, S.; Loffier, W.; Wegener, O.H.; Ernst, H.","year":"1986","unstructured":"Ahuja S, Loffier W, Wegener OH, Ernst H. Tuberous sclerosis with angiomyolipoma and metastasised hypernephroma. Urology 1986;28:413-19.","journal-title":"Urology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/j.1399-0004.1989.tb02924.x","article-title":"Tuberous sclerosis and the relation with renal angiomyolipoma. A genetic study on the clinical aspects","volume":"35","author":"van Baal JG; P, Fleury; H, Brummelkamp","year":"1989","unstructured":"van Baal JG, Fleury P, Brummelkamp H. Tuberous sclerosis and the relation with renal angiomyolipoma. A genetic study on the clinical aspects. Clin Genet 1989;35:167-73.","journal-title":"Clin Genet"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.32.11.848","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T05:36:18Z","timestamp":1760765778000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.32.11.848"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,11]]},"references-count":22,"journal-issue":{"issue":"11","published-online":{"date-parts":[[1995,11,1]]},"published-print":{"date-parts":[[1995,11]]}},"alternative-id":["10.1136\/jmg.32.11.848"],"URL":"https:\/\/doi.org\/10.1136\/jmg.32.11.848","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,11]]}}}