Birt-Hogg-Dube syndrome (BHD) is an autosomal dominant neoplasia syndrome characterized mainly by benign skin tumors, and to a lesser extent, renal tumors and spontaneous pneumothorax. To map the BHD locus, we performed a genome-wide linkage analysis using polymorphic microsatellite markers on a large Swedish BHD family. Evidence of linkage was identi®ed on chromosome 17p12-q11.2, with a maximum LOD score of 3.58 for marker D17S1852. Further haplotype analysis de®ned a *35 cM candidate interval between the two¯anking markers, D17S1791 and D17S798. This information will facilitate the identi®cation of the BHD gene, leading to the understanding of its underlying molecular etiology. Oncogene (2001) 20, 5239 ± 5242.

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In this study 44 parathyroid tumors from 26 sporadic cases, 10 cases previously given irradiation to the neck, and 8 familial cases were screened for sequence copy number alterations by comparative genomic hybridization. In the sporadic adenomas, commonly occurring minimal regions of loss could be defined to chromosome 11 (38%), 15q15-qter (27%), and 1p34-pter (19%), whereas gains preferentially involved 19p13.2-pter (15%) and 7pter-qter (12%). Multiple aberrations were found in sporadic tumors with a somatic mutation and/or loss of heterozygosity of the MEN1 gene. The irradiation-associated tumors also showed multiple comparative genomic hybridization alterations and frequent losses of 11q (50%), and subsequent analysis of the MEN1 gene demonstrated mutations in 4 of 8 cases (50%). The adenomas from familial cases showed few alterations, and in 3 of these tumors a gain of 19p13.2-pter was seen as the only aberration. In this study numerical copy number alterations were frequently detected in sporadic and irradiation-associated parathyroid adenomas, although these tumors are benign. The majority of these alterations were found in tumors with confirmed involvement of the MEN1 gene locus in agreement with a role of the MEN1 gene in genomic stability. Furthermore, the frequent occurrence of MEN1 mutations (50%) in irradiation-associated parathyroid tumors suggests that inactivation of the MEN1 gene is an important genetic alteration involved in the development of parathyroid tumors in postirradiation patients.

These data confirm the importance of collagen 4A4 as a component in the structural integrity of the glomerular basement membrane and confirm the phenotypic and genetic heterogeneity of collagen disorders.