title: Polyclonality of Parathyroid Tumors in Neonatal Severe Hyperparathyroidism.
abstract: Neonatal severe hyperparathyroidism (NSHPT) is a rare disorder characterized by major hypercalcemia, elevated parathyroid hormone levels, and marked enlargement of multiple parathyroid glands, usually associated with germline mutations in the calcium receptor gene CASR. However, little is known about the outgrowth of parathyroid tumors in NSHPT, including whether they represent monoclonal or polyclonal expansions. We sought to examine the clonality of parathyroid tissues resected from a patient with NSHPT and biallelic CASR mutations. DNA from two distinct parathyroid tumors resected from a girl with NSHPT, plus polyclonal/monoclonal control samples, were subjected to analyses of clonality by two independent methods, X-chromosome inactivation analysis at the androgen receptor locus (HUMARA) and BAC array comparative genomic hybridization (CGH). Both parathyroid tumor samples revealed polyclonal patterns by X-inactivation analysis, with polyclonal and monoclonal controls yielding the expected patterns. Similarly, by BAC array CGH, neither parathyroid sample contained monoclonal copy number changes and both appeared identical to the patient-matched polyclonal controls. Our observations provide direct experimental evidence that the markedly enlarged parathyroid tumors in the setting of NSHPT constitute polyclonal, generalized hyperplastic growths rather than monoclonal neoplasms.
authors.affiliation: Center for Molecular Medicine, University of Connecticut School of Medicine, Farmington, CT, USA.
authors.forename: Kristin R
authors.initials: KR
authors.lastname: Corrado
authors.affiliation: Pediatric Endocrinology Laboratory, Center for Investigation in Pediatrics, Department of Pediatrics, Faculty of Medical Science, State University of Campinas, São Paulo, Brazil.
authors.forename: Simone Caixeta
authors.initials: SC
authors.lastname: Andrade
authors.affiliation: Center for Molecular Medicine, University of Connecticut School of Medicine, Farmington, CT, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Bellizzi
authors.affiliation: Pediatric Endocrinology Laboratory, Center for Investigation in Pediatrics, Department of Pediatrics, Faculty of Medical Science, State University of Campinas, São Paulo, Brazil.
authors.forename: Lilia
authors.initials: L
authors.lastname: D'Souza-Li
authors.affiliation: Center for Molecular Medicine, University of Connecticut School of Medicine, Farmington, CT, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Arnold
mesh_terms: D055028:Comparative Genomic Hybridization; D005260:Female; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000235:genetics / Q000473:pathology; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000235:genetics / Q000473:pathology; D008297:Male; D009154:Mutation; D010282:Parathyroid Neoplasms / Q000235:genetics / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics*; D044169:Receptors, Calcium-Sensing / Q000235:genetics*
chemical_list: C410798:AR protein, human; C095550:CASR protein, human; D011944:Receptors, Androgen; D044169:Receptors, Calcium-Sensing
keywords: CALCIUM-SENSING RECEPTOR; CASR; FAMILIAL HYPERPARATHYROIDISM; PARATHYROID NEOPLASIA; PTH