title: Genetic analysis of lithium-associated parathyroid tumors.
abstract: OBJECTIVE
  The aim of this study was to determine the primary genetic events that may underlie the formation of parathyroid tumors in patients with lithium-associated hyperparathyroidism (HPT).
  
  
  METHODS
  Comparative genomic hybridization (CGH), loss of heterozygosity (LOH) and multiple endocrine neoplasia type 1 gene (MEN1) mutation analysis were used to analyze twelve parathyroid tumors from nine patients with lithium-associated HPT. For comparison, CGH was also carried out in a non-lithium-associated group of thirteen sporadic parathyroid tumors.
  
  
  RESULTS
  A higher prevalence of multiglandular disease in the lithium-associated HPT patients compared with the idiopathic sporadic patients was observed (Fisher's exact test, P=0.02). CGH alterations were detected in four lithium-associated parathyroid tumors, involving loss at 1p, 11, 15q, 22q and gain of the X chromosome. In addition, one of these four cases exhibited LOH at 11q13 and was found to contain a novel somatic MEN1 mutation (c.1193insTAC). Although fewer lithium-associated parathyroid tumors were shown to contain genetic alterations compared with the sporadic parathyroid tumors, the changes detected were those frequently associated with both familial and sporadic parathyroid tumorigenesis.
  
  
  CONCLUSIONS
  This is, to our knowledge, the first genetic analysis of parathyroid tumors in lithium-associated HPT patients. Our data indicated that the majority of lithium-associated parathyroid tumors do not contain gross chromosomal alterations and suggest that in most cases the tumorigenic pathway is independent of MEN1 and genes at 1p34.3-pter and 1q21-q32. It is possible that other discrete genetic alterations or epigenetic changes, not screened for in this study, could also be responsible for parathyroid tumorigenesis in lithium-associated HPT.
authors: Cancer Genetics Unit, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia.
authors: T
authors: T
authors: Dwight
authors: S
authors: S
authors: Kytölä
authors: B T
authors: BT
authors: Teh
authors: G
authors: G
authors: Theodosopoulos
authors: A L
authors: AL
authors: Richardson
authors: J
authors: J
authors: Philips
authors: S
authors: S
authors: Twigg
authors: L
authors: L
authors: Delbridge
authors: D J
authors: DJ
authors: Marsh
authors: A E
authors: AE
authors: Nelson
authors: C
authors: C
authors: Larsson
authors: B G
authors: BG
authors: Robinson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000139:chemically induced; D008094:Lithium / Q000009:adverse effects*; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009377:Multiple Endocrine Neoplasia / Q000453:epidemiology; D009363:Neoplasm Proteins / Q000235:genetics; D009693:Nucleic Acid Hybridization; D010282:Parathyroid Neoplasms / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics*; D015995:Prevalence; D011518:Proto-Oncogene Proteins
chemical_list: C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D008094:Lithium