{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T12:51:44Z","timestamp":1761742304582,"version":"3.37.3"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2004,3,29]],"date-time":"2004-03-29T00:00:00Z","timestamp":1080518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100002794","name":"Swedish Cancer Society","doi-asserted-by":"publisher","award":["3911"],"award-info":[{"award-number":["3911"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006310","name":"Swedish Medical Research Council","doi-asserted-by":"publisher","award":["5220"],"award-info":[{"award-number":["5220"]}],"id":[{"id":"10.13039\/501100006310","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003849","name":"IB & A Lundberg Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003849","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Assar Gabrielsson Foundation"},{"DOI":"10.13039\/501100005689","name":"G\u00f6teborg Medical Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005689","id-type":"DOI","asserted-by":"publisher"}]},{"name":"King Gustav V Jubilee Clinic Cancer Fund, G\u00f6teborg, Sahlgrenska Hospital Research Funds, Camilla Landgren Memorial Fund, Department of Research and Development, County Hospital, Varberg, Sweden"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,5,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Multiple endocrine neoplasia type 2A (MEN2A) is caused by missense mutations in the RET proto-oncogene on chromosome 10. This paper reports the phenotypic expression of a family with MEN2A, in which serine substitutes for cysteine at codon 618 in exon 10 of the RET gene. It was first claimed that medullary thyroid cancer (MTC) with this rare mutation led to mild disease; this has recently been updated to intermediate\u2013high risk, based on stratified genetic information.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The family was mapped over six generations. In 1971 family members were invited to join a screening programme. Genetic testing was started in 1994.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Twenty-two individuals with MTC were identified, 16 by the screening programme. One screened patient had a phaeochromocytoma and four had hyperparathyroidism. At surgery for MTC 12 patients had local tumour metastases and two young patients also had liver metastases. No screened patient died from MTC during a mean observation time of 19 years. Six other family members were diagnosed with MTC by signs and symptoms, five of whom died from MTC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Because of the great interindividual differences in tumour aggressiveness within the family it is impossible to predict whether an individual gene carrier will have an aggressive MTC or not. This unpredictability is an additional argument, besides those obtained in stratified genetic studies, for operating on gene carriers at young age.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/bjs.4457","type":"journal-article","created":{"date-parts":[[2004,3,29]],"date-time":"2004-03-29T16:02:15Z","timestamp":1080576135000},"page":"713-718","source":"Crossref","is-referenced-by-count":20,"title":["Phenotypic expression of a family with multiple endocrine neoplasia type 2A due to a <i>RET<\/i> mutation at codon 618"],"prefix":"10.1093","volume":"91","author":[{"given":"S","family":"Lindskog","sequence":"first","affiliation":[{"name":"Department of Surgery, Varberg Hospital, Varberg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Lundberg Laboratory for Cancer Research, Department of Pathology, Sahlgrenska University Hospital, G\u00f6teborg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Jansson","sequence":"additional","affiliation":[{"name":"Lundberg Laboratory for Cancer Research, Department of Surgery, Sahlgrenska University Hospital, G\u00f6teborg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Lundberg Laboratory for Cancer Research, Department of Surgery, Sahlgrenska University Hospital, G\u00f6teborg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A-C","family":"Illerskog","sequence":"additional","affiliation":[{"name":"Lundberg Laboratory for Cancer Research, Department of Pathology, Sahlgrenska University Hospital, G\u00f6teborg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Ysander","sequence":"additional","affiliation":[{"name":"Department of Medicine, Varberg Hospital, Varberg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Ahlman","sequence":"additional","affiliation":[{"name":"Lundberg Laboratory for Cancer Research, Department of Surgery, Sahlgrenska University Hospital, G\u00f6teborg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L-E","family":"Tisell","sequence":"additional","affiliation":[{"name":"Lundberg Laboratory for Cancer Research, Department of Surgery, Sahlgrenska University Hospital, G\u00f6teborg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2004,3,29]]},"reference":[{"key":"2021070907140529700_bib1","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.7326\/0003-4819-63-6-1027","article-title":"Familial amyloid-producing medullary thyroid carcinoma and pheochromocytoma. A distinct genetic entity","volume":"63","author":"Schimke","year":"1965","journal-title":"Ann Intern Med"},{"key":"2021070907140529700_bib2","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1097\/00005792-196809000-00001","article-title":"Study of a kindred with pheochromocytoma, medullary thyroid carcinoma, hyperparathyroidism and Cushing's disease: multiple endocrine neoplasia, type 2","volume":"47","author":"Steiner","year":"1968","journal-title":"Medicine (Baltimore)"},{"key":"2021070907140529700_bib3","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/328527a0","article-title":"A linked genetic marker for multiple endocrine neoplasia type 2A on chromosome 10","volume":"328","author":"Mathew","year":"1987","journal-title":"Nature"},{"key":"2021070907140529700_bib4","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/328528a0","article-title":"Assignment of multiple endocrine neoplasia syndrome type 2A to chromosome 10 by linkage","volume":"328","author":"Simpson","year":"1987","journal-title":"Nature"},{"key":"2021070907140529700_bib5","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1093\/hmg\/2.7.851","article-title":"Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC","volume":"2","author":"Donis-Keller","year":"1993","journal-title":"Hum Mol Genet"},{"key":"2021070907140529700_bib6","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/363458a0","article-title":"Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A","volume":"363","author":"Mulligan","year":"1993","journal-title":"Nature"},{"key":"2021070907140529700_bib7","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1073\/pnas.91.4.1579","article-title":"Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B","volume":"91","author":"Carlson","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021070907140529700_bib8","first-page":"1736s","article-title":"The phenotypes associated with ret mutations in the multiple endocrine neoplasia type 2 syndrome","volume":"59","author":"Ponder","year":"1999","journal-title":"Cancer Res"},{"key":"2021070907140529700_bib9","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1001\/jama.1996.03540190047028","article-title":"The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET Mutation Consortium analysis","volume":"276","author":"Eng","year":"1996","journal-title":"JAMA"},{"key":"2021070907140529700_bib10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3109\/02841869009089985","article-title":"Incidence of sporadic and familial medullary thyroid carcinoma in Sweden 1959 through 1981. A nationwide study in 126 patients. Swedish MCT Study Group","volume":"29","author":"Bergholm","year":"1990","journal-title":"Acta Oncol"},{"key":"2021070907140529700_bib11","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1097\/00005792-198411000-00001","article-title":"Medullary carcinoma of the thyroid. A study of the clinical features and prognostic factors in 161 patients","volume":"63","author":"Saad","year":"1984","journal-title":"Medicine (Baltimore)"},{"key":"2021070907140529700_bib12","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/S0002-9343(96)00330-0","article-title":"Familial medullary thyroid carcinoma: not a distinct entity? Genotype\u2013phenotype correlation in a large family","volume":"101","author":"Moers","year":"1996","journal-title":"Am J Med"},{"key":"2021070907140529700_bib13","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1507\/endocrj.43.25","article-title":"A family of multiple endocrine neoplasia type 2A: genetic analysis and clinical features","volume":"43","author":"Morita","year":"1996","journal-title":"Endocr J"},{"key":"2021070907140529700_bib14","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1093\/jjco\/28.10.590","article-title":"Genotype\u2013phenotype correlation of patients with multiple endocrine neoplasia type 2 in Japan","volume":"28","author":"Egawa","year":"1998","journal-title":"Jpn J Clin Oncol"},{"key":"2021070907140529700_bib15","first-page":"531","volume-title":"Surgical Endocrinology","author":"Kikumori","year":"2001"},{"key":"2021070907140529700_bib16","doi-asserted-by":"crossref","first-page":"5658","DOI":"10.1210\/jcem.86.12.8070","article-title":"Consensus. Guidelines for diagnosis and therapy of MEN type1 and type 2","volume":"86","author":"Brandi","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2021070907140529700_bib17","first-page":"1104","article-title":"Genotype\u2013phenotype correlations in hereditary medullary thyroid carcinoma: oncological features and biochemical properties","volume":"86","author":"Machens","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2021070907140529700_bib18","first-page":"60","article-title":"Reoperation in the treatment of asymptomatic metastasizing medullary thyroid carcinoma","volume":"99","author":"Tisell","year":"1986","journal-title":"Surgery"},{"key":"2021070907140529700_bib19","first-page":"35","volume-title":"UICC TNM Classification of Malignant Tumours","author":"Hermanek","year":"1992","edition":"4th"},{"key":"2021070907140529700_bib20","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1001\/jama.281.17.1587","article-title":"Adrenal and extra-adrenal pheochromocytomas in a family with germline RET V804L mutation","volume":"281","author":"Nilsson","year":"1999","journal-title":"JAMA"},{"key":"2021070907140529700_bib21","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1002\/1097-0142(19880215)61:4<806::AID-CNCR2820610428>3.0.CO;2-G","article-title":"Prognostic factors in medullary thyroid carcinomas. Survival in relation to age, sex, stage, histology, immunocytochemistry, and DNA content","volume":"61","author":"Schr\u00f6der","year":"1988","journal-title":"Cancer"},{"key":"2021070907140529700_bib22","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1056\/NEJM199409293311302","article-title":"Clinical screening as compared with DNA analysis in families with multiple endocrine neoplasia type 2A","volume":"331","author":"Lips","year":"1994","journal-title":"N Engl J Med"},{"key":"2021070907140529700_bib23","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1056\/NEJM198802253180804","article-title":"The clinical outcome of prospective screening for multiple endocrine neoplasia type 2a. An 18-year experience","volume":"318","author":"Gagel","year":"1988","journal-title":"N Engl J Med"}],"container-title":["British Journal of Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbjs.4457","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/academic.oup.com\/bjs\/article-pdf\/91\/6\/713\/36729723\/bjs4457.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/bjs\/article-pdf\/91\/6\/713\/36729723\/bjs4457.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T16:32:57Z","timestamp":1625848377000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bjs\/article\/91\/6\/713\/6150954"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,3,29]]},"references-count":23,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2004,3,29]]},"published-print":{"date-parts":[[2004,5,17]]}},"URL":"https:\/\/doi.org\/10.1002\/bjs.4457","relation":{},"ISSN":["0007-1323","1365-2168"],"issn-type":[{"type":"print","value":"0007-1323"},{"type":"electronic","value":"1365-2168"}],"subject":[],"published-other":{"date-parts":[[2004,6]]},"published":{"date-parts":[[2004,3,29]]}}}