{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T12:12:24Z","timestamp":1792239144341,"version":"4.4.0"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,3,31]],"date-time":"2017-03-31T00:00:00Z","timestamp":1490918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a familial cancer syndrome associated with the development of cutaneous and uterine leiomyomas, and an aggressive form of type 2 papillary kidney cancer. HLRCC is characterized by germline mutation of the <jats:italic>FH<\/jats:italic> gene. This study evaluated the prevalence and clinical phenotype of <jats:italic>FH<\/jats:italic> deletions in HLRCC patients. Patients with phenotypic manifestations consistent with HLRCC who lacked detectable germline <jats:italic>FH<\/jats:italic> intragenic mutations were investigated for <jats:italic>FH<\/jats:italic> deletion. A series of 28 patients from 13 families were evaluated using a combination of a comparative genomic hybridization (CGH) array and\/or CLIA\u2010approved <jats:italic>FH<\/jats:italic> deletion\/duplication analyses. Thirteen distinct germline deletions were identified in the 13 UOB families, including 11 complete <jats:italic>FH<\/jats:italic> gene deletions and 2 partial <jats:italic>FH<\/jats:italic> gene deletions. The size of eight evaluated complete <jats:italic>FH<\/jats:italic> deletions varied from \u223c4.74 Mb to 249 kb, with all deletions resulting in additional gene losses. Two partial <jats:italic>FH<\/jats:italic> gene deletions were identified, with one resulting in loss of exon 1 and the upstream region of the <jats:italic>FH<\/jats:italic> gene only. Kidney cancer was diagnosed in 9 (32%) of 28 patients and 7 (54%) of 13 families possessing either complete or partial <jats:italic>FH<\/jats:italic> deletions. Cutaneous and uterine leiomyomas were observed at similar rates to those in <jats:italic>FH<\/jats:italic> point mutation families. Complete or partial <jats:italic>FH<\/jats:italic> gene alterations in HLRCC families are associated with all of the canonical HLRCC manifestations, including type 2 papillary kidney cancer and should be screened for in any patient at\u2010risk for this disorder.<\/jats:p>","DOI":"10.1002\/gcc.22452","type":"journal-article","created":{"date-parts":[[2017,2,14]],"date-time":"2017-02-14T23:02:43Z","timestamp":1487113363000},"page":"484-492","source":"Crossref","is-referenced-by-count":28,"title":["Comprehensive genomic and phenotypic characterization of germline <i>FH<\/i> deletion in hereditary leiomyomatosis and renal cell carcinoma"],"prefix":"10.1002","volume":"56","author":[{"given":"Cathy D.","family":"Vocke","sequence":"first","affiliation":[{"name":"Urologic Oncology Branch Center for Cancer Research, National Cancer Institute, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Ricketts","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch Center for Cancer Research, National Cancer Institute, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Merino","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology Center for Cancer Research, National Cancer Institute, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramaprasad","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch Center for Cancer Research, National Cancer Institute, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam R.","family":"Metwalli","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch Center for Cancer Research, National Cancer Institute, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay A.","family":"Middelton","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch Center for Cancer Research, National Cancer Institute, National Institutes of Health Bethesda Maryland USA"},{"name":"Clinical Research Directorate\/Clinical Monitoring Research Program Leidos Biomedical Research, Inc, NCI Campus at Frederick Frederick Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Peterson","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch Center for Cancer Research, National Cancer Institute, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youfeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch Center for Cancer Research, National Cancer Institute, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7983-3109","authenticated-orcid":false,"given":"W. 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