{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:58:39Z","timestamp":1788436719387,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2007,2,26]],"date-time":"2007-02-26T00:00:00Z","timestamp":1172448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2007,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The Birt\u2013Hogg\u2013Dub\u00e9 (<jats:italic>BHD<\/jats:italic>) gene is responsible for BHD syndrome, a rare autosomal dominant disease, characterized by benign hair follicle tumours, spontaneous pneumothorax and renal neoplasms with diverse histology. To elucidate its involvement in the development of renal neoplasms, we examined a total of 100 sporadic renal tumours with various histological subtypes for <jats:italic>BHD<\/jats:italic> mutation by SSCP\u2010sequencing analyses. We found one germline insertion mutation in the C8 hotspot of exon 11 (c.1733insC), which is known to have a strong association with renal tumour occurrence. The germline\u2010mutated patient suffered from solitary renal cell carcinoma (RCC) but did not have any other <jats:italic>BHD<\/jats:italic> manifestations or family history. The tumour revealed heterogeneous cytomorphology, mainly a mixture of eosinophilic and focally clear cells with tubulopapillary architecture. In this tumour, both <jats:italic>BHD<\/jats:italic> alleles were inactivated by germline mutation concomitant with loss of heterozygosity, and the amount of <jats:italic>BHD<\/jats:italic> mRNA detected by real\u2010time quantitative PCR (RQ\u2010PCR) was very low. Renal tumour subtype\/nephron segment\u2010specific gene expression detected by RQ\u2010PCR demonstrated that the tumour expressed relatively high amounts of \u03b1\u2010methylacyl\u2010CoA racemase (<jats:italic>AMACR<\/jats:italic>) and the <jats:italic>KIT<\/jats:italic> oncogene, but relatively low amounts of carbonic anhydrase IX (<jats:italic>CA9<\/jats:italic>), aquaporin 1 (<jats:italic>AQP1<\/jats:italic>), claudin 7 (<jats:italic>CLDN7<\/jats:italic>), parvalbumin (<jats:italic>PVALB<\/jats:italic>), chloride channel Kb (<jats:italic>CLCNKB<\/jats:italic>) and 11\u2010\u03b2\u2010hydroxysteroid dehydrogenase 2 (<jats:italic>HSD11B2<\/jats:italic>), suggesting diverse mRNA signatures. Further clustering analysis of 88 renal tumours based on expression of these eight genes sub\u2010classified the tumour as close to oncocytomas and chromophobe RCCs, which are considered distal nephron\u2010associated tumours. These data suggest that somatic mutation of <jats:italic>BHD<\/jats:italic> is relatively rare in Japanese patients. The <jats:italic>BHD<\/jats:italic>\u2010mutated RCC identified in this study, which exhibits heterogeneous biological features in both morphology and gene expression signatures, seems to deviate from our current understanding of renal tumour classification. Copyright \u00a9 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2139","type":"journal-article","created":{"date-parts":[[2007,2,26]],"date-time":"2007-02-26T08:07:20Z","timestamp":1172477240000},"page":"524-531","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Identification and characterization of Birt\u2013Hogg\u2013Dub\u00e9 associated renal 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