{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:34:27Z","timestamp":1781105667060,"version":"3.54.1"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"3","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,2,5]]},"abstract":"<jats:p>\n                    Few data exist on somatic mutation in the epithelial cell lineages that play a central role in human biology and disease. To delineate the \u201clandscape\u201d of somatic mutation in a human epithelial cell lineage, we determined the frequency and molecular nature of somatic mutations occurring\n                    <jats:italic>in vivo<\/jats:italic>\n                    in the X-linked\n                    <jats:italic>HPRT<\/jats:italic>\n                    gene of kidney tubular epithelial cells. Kidney epithelial mutants were frequent (range 0.5 to 4.2 \u00d7 10\n                    <jats:sup>\u22124<\/jats:sup>\n                    ) and contained a high proportion of unreported\n                    <jats:italic>HPRT<\/jats:italic>\n                    base substitutions, \u22121-bp deletions and multiple mutations. This spectrum of somatic mutation differed from\n                    <jats:italic>HPRT<\/jats:italic>\n                    mutations identified in human peripheral blood T lymphocytes and from germ-line\n                    <jats:italic>HPRT<\/jats:italic>\n                    mutations identified in Lesch\u2013Nyhan syndrome or hyperuricemia patients. Our results indicate that DNA damage and mutagenesis may have unusual or mechanistically interesting features in kidney tubular epithelium, and that somatic mutation may play a more important role in human kidney disease than has been previously appreciated.\n                  <\/jats:p>","DOI":"10.1073\/pnas.032655699","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:36:44Z","timestamp":1027679804000},"page":"1437-1442","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":39,"title":["The unexpected landscape of\n                    <i>in vivo<\/i>\n                    somatic mutation in a human epithelial cell lineage"],"prefix":"10.1073","volume":"99","author":[{"given":"Lorel M.","family":"Colgin","sequence":"first","affiliation":[{"name":"Departments of Pathology, Biostatistics, and Genome Sciences, University of Washington, Box 357705, Seattle, WA 98195-7705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alden F. M.","family":"Hackmann","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Biostatistics, and Genome Sciences, University of Washington, Box 357705, Seattle, WA 98195-7705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary J.","family":"Emond","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Biostatistics, and Genome Sciences, University of Washington, Box 357705, Seattle, WA 98195-7705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Raymond J.","family":"Monnat","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Biostatistics, and Genome Sciences, University of Washington, Box 357705, Seattle, WA 98195-7705"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,1,29]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"1138","volume-title":"Molecular Biology of the Cell","author":"Alberts B","year":"1994","unstructured":", eds B Alberts, D Bray, J Lewis, M Raff, K Roberts, J D Watson (Garland, New York) Molecular Biology of the Cell, pp. 1138\u20131193 (1994)."},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.2.215"},{"key":"e_1_3_3_3_2","volume-title":"Ph.D. thesis","author":"Colgin L M","year":"1997","unstructured":"L M Colgin Ph.D. thesis (Univ. of Washington, Seattle, 1997)."},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(94)90320-4"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/17.9.1871"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2280(1997)30:4<371::AID-EM2>3.0.CO;2-M"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/19.4.557"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0027-5107(99)00176-1"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1383-5718(00)00039-5"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1999)13:6<504::AID-HUMU15>3.0.CO;2-6"},{"key":"e_1_3_3_11_2","first-page":"2537","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Jinnah H A","year":"2001","unstructured":"H A Jinnah, T Friedmann The Metabolic and Molecular Bases of Inherited Disease, eds C R Scriver, A L Beaudet, W S Sly, D Valle (McGraw\u2013Hill, New York), pp. 2537\u20132570 (2001)."},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(90)90545-6"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(200001)15:1<2::AID-HUMU2>3.0.CO;2-Y"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.2.477"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(90)90493-E"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/136.1.403"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1993.1255"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/26.1.198"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M007096200"},{"key":"e_1_3_3_20_2","first-page":"124","volume":"27","author":"Reuter V E","year":"2000","unstructured":"V E Reuter, J C Presti Semin Oncol 27, 124\u2013137 (2000).","journal-title":"Semin Oncol"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1383-5742(00)00052-1"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0027-5107(00)00090-7"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5465.514"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2280(1998)32:2<188::AID-EM16>3.0.CO;2-Y"},{"key":"e_1_3_3_25_2","volume-title":"The Genetic Basis of Human Cancer","author":"Vogelstein B","year":"1998","unstructured":"B Vogelstein, K W Kinzler The Genetic Basis of Human Cancer (McGraw\u2013Hill, New York, 1998)."},{"key":"e_1_3_3_26_2","volume-title":"DNA Alterations in Cancer: Genetic and Epigenetic Changes","author":"Ehrlich M","year":"1999","unstructured":"M Ehrlich DNA Alterations in Cancer: Genetic and Epigenetic Changes (Eaton, Natick, MA, 1999)."},{"key":"e_1_3_3_27_2","first-page":"333","volume-title":"Molecular Cell Genetics","author":"Fenwick R G","year":"1985","unstructured":"R G Fenwick Molecular Cell Genetics, ed M Gottesman (Wiley, New York), pp. 333\u2013373 (1985)."},{"key":"e_1_3_3_28_2","first-page":"215","volume-title":"Brenner and Rector's The Kidney","author":"Gullans S R","year":"2000","unstructured":"S R Gullans Brenner and Rector's The Kidney, ed B M Brenner (Saunders, Philadelphia), pp. 215\u2013246 (2000)."},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1383-5718(00)00058-9"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0027-5107(98)00066-9"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(01)02239-9"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1383-5742(00)00047-8"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.69.1.497"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/35040051"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)00145-3"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00509-8"},{"key":"e_1_3_3_37_2","first-page":"122","volume":"26","author":"Cuppage F E","year":"1972","unstructured":"F E Cuppage, M Chiga, A Tate Lab Invest 26, 122\u2013126 (1972).","journal-title":"Lab Invest"},{"key":"e_1_3_3_38_2","first-page":"981","volume-title":"The Biology of Epithelial Cell Populations","author":"Wright N","year":"1984","unstructured":", eds N Wright, M Alison (Clarendon, Oxford) The Biology of Epithelial Cell Populations, pp. 981\u20131003 (1984)."},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.112.2.489"},{"key":"e_1_3_3_40_2","first-page":"2571","volume-title":"The Kidney: Physiology and Pathophysiology","author":"Choudhury D","year":"2000","unstructured":"D Choudhury, B Palmer, M Levi The Kidney: Physiology and Pathophysiology, eds D W Seldin, G Giebisch (Lippincott Williams & Wilkins, Philadelphia), pp. 2571\u20132595 (2000)."},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.1999.2896"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1097\/00041552-199905000-00008"},{"key":"e_1_3_3_43_2","first-page":"41","volume":"15","author":"Grignon D J","year":"1998","unstructured":"D J Grignon, J N Eble Semin Diagnostic Pathol 15, 41\u201353 (1998).","journal-title":"Semin Diagnostic Pathol"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1998)11:1<1::AID-HUMU1>3.0.CO;2-O"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.032655699","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T09:08:12Z","timestamp":1649754492000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.032655699"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,1,29]]},"references-count":44,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2002,2,5]]}},"alternative-id":["10.1073\/pnas.032655699"],"URL":"https:\/\/doi.org\/10.1073\/pnas.032655699","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,1,29]]},"assertion":[{"value":"2001-08-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-12-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}