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Initiated 12\u00a0years ago, this protocol enrolled 724 subjects from 147 unrelated families with either \u22652 affected men (<jats:italic>n<\/jats:italic>\u00a0=\u00a090) with <jats:styled-content style=\"fixed-case\">TGCT<\/jats:styled-content> or a proband with bilateral <jats:styled-content style=\"fixed-case\">TGCT<\/jats:styled-content> and a negative family history for this cancer (<jats:italic>n<\/jats:italic>\u00a0=\u00a057). Data were collected directly from 162 subjects evaluated at the <jats:styled-content style=\"fixed-case\">NIH<\/jats:styled-content> Clinical Center, and 562 subjects provided information from their home communities (Field Cohort). The primary study aims included (i) ascertaining, enrolling eligible <jats:styled-content style=\"fixed-case\">FTGCT<\/jats:styled-content> kindred, (ii) characterizing the clinical phenotype of multiple\u2010case families, (iii) identifying the underlying genetic mechanism for <jats:styled-content style=\"fixed-case\">TGCT<\/jats:styled-content> susceptibility in families, (iv) evaluating counseling, psychosocial, and behavioral issues resulting from membership in an <jats:styled-content style=\"fixed-case\">FTGCT<\/jats:styled-content> family, and (v) creating an annotated biospecimen repository to permit subsequent translational research studies. Noteworthy findings include (i) documenting the epidemiologic similarities between familial and sporadic <jats:styled-content style=\"fixed-case\">TGCT<\/jats:styled-content>, (ii) demonstrating significantly younger age\u2010at\u2010diagnosis for familial vs. sporadic <jats:styled-content style=\"fixed-case\">TGCT<\/jats:styled-content>, (iii) absence of a dysmorphic phenotype in affected family members, (iv) shifting the focus of gene discovery from a search for rare, highly penetrant susceptibility variants to the hypothesis that multiple, more common, lower penetrance genes underlie <jats:styled-content style=\"fixed-case\">TGCT<\/jats:styled-content> genetic risk, (v) implicating testicular microlithiasis in <jats:styled-content style=\"fixed-case\">FTGCT<\/jats:styled-content> risk, and (vi) observing that aberrant methylation may contribute to <jats:styled-content style=\"fixed-case\">FTGCT<\/jats:styled-content> risk. A clinically based, biospecimen\u2010intensive, multidisciplinary research strategy has provided novel, valuable insights into the etiology of <jats:styled-content style=\"fixed-case\">FTGCT<\/jats:styled-content>, and created a research resource which will support <jats:styled-content style=\"fixed-case\">FTGCT<\/jats:styled-content> clinical and laboratory studies for years to come.<\/jats:p>","DOI":"10.1111\/andr.294","type":"journal-article","created":{"date-parts":[[2014,10,10]],"date-time":"2014-10-10T02:08:00Z","timestamp":1412906880000},"page":"47-58","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Familial testicular germ cell tumors (FTGCT) \u2013 overview of a multidisciplinary etiologic study"],"prefix":"10.1111","volume":"3","author":[{"given":"M. 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