title: Angiomyolipoma have common mutations in TSC2 but no other common genetic events.
abstract: Renal angiomyolipoma are part of the PEComa family of neoplasms, and occur both in association with Tuberous Sclerosis Complex (TSC) and independent of that disorder. Previous studies on the molecular genetic alterations that occur in angiomyolipoma are very limited. We evaluated 9 angiomyolipoma for which frozen tissue was available from a consecutive surgical series. Seven of 8 samples subjected to RT-PCR-cDNA sequencing showed mutations in TSC2; none showed mutations in TSC1 or RHEB. Six of the seven mutations were deletions. We searched for 983 activating and inactivating mutations in 115 genes, and found none in these tumors. Similarly analysis for genomic regions of loss or gain, assessed by Affymetrix SNP6.0 analysis, showed no abnormalities. Loss of heterozygosity in the TSC2 region was commonly seen, except in patients with low frequency TSC2 mutations. We conclude that sporadic renal angiomyolipoma usually have mutations in TSC2, but not TSC1 or RHEB, and have no other common genomic events, among those we searched for. However, chromosomal translocations and gene fusion events were not assessed here. TSC2 inactivation by mutation is a consistent and likely necessary genetic event in the pathogenesis of most angiomyolipoma.
authors.affiliation: Translational Medicine Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Qin
authors.forename: Vineeta
authors.initials: V
authors.lastname: Bajaj
authors.forename: Izabela
authors.initials: I
authors.lastname: Malinowska
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
authors.forename: Laura
authors.initials: L
authors.lastname: MacConaill
authors.forename: Chin-Lee
authors.initials: CL
authors.lastname: Wu
authors.forename: David J
authors.initials: DJ
authors.lastname: Kwiatkowski
mesh_terms: D000328:Adult; D000368:Aged; D018207:Angiomyolipoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D000076205:Ras Homolog Enriched in Brain Protein; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D009479:Neuropeptides; C490211:RHEB protein, human; D012333:RNA, Messenger; D000076205:Ras Homolog Enriched in Brain Protein; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D020559:Monomeric GTP-Binding Proteins