Chromosomal aberrations, the consequence of refractory hyperparathyroidism: its relationship with biochemical parameters.
BACKGROUND
It has been shown that refractory hyperparathyroidism (HPT) correlates biologically with a monoclonal true neoplasm, but the chromosomal changes and their relationship with biochemical variables such as high levels of phosphate, low levels of calcium (Ca), and calcitriol deficiency are still in need of a deeper analysis.


METHODS
Comparative genomic hybridization was used to scan for DNA copy number changes in two groups of samples: 57 glands from refractory secondary HPT and 28 glands from refractory HPT after kidney transplantation. Biochemical HPT-related parameters from these patients were collected and analyzed.


RESULTS
Sixty-one percent of the glands from dialysis patients and 53.6% of the glands from transplanted patients suffering severe secondary hyperparathyroidism had clonal chromosomal imbalances. Losses were far more common than gains. The most recurrent changes were losses of 1p (71%), monosomies of chromosomes 19 and 22 (45%), and losses of 20q (44%) and 16p (42%). The most frequent gains were 5q, 6q, and 13q. Biochemical parameters suggested that Ca excess is related to the development of these chromosomal aberrations, although it is not known if it is by playing a role in producing the alterations or merely as a reflection of HPT severity. Phosphate levels, despite their known effect in increasing the proliferation of the parathyroid glands, were not related to the chromosomal aberrations found in severe secondary HPT.


CONCLUSIONS
Clonal recurrent chromosomal changes are present in more than half of the glands from patients with refractory HPT, which undergo extreme biochemical levels in hyperparathyroidism effectors. These changes support the idea of the monoclonal neoplastic nature of this disorder.
Afonso
Sandra
S
Cytogenetic Unit, Hospital Universitario de Canarias, Tenerife, Spain; Bone and Mineral Research Unit, Hospital Central de Asturias, Oviedo, Spain.
Santamaría
Iñigo
I
Guinsburg
Martín E
ME
Gómez
Ana Otero
AO
Miranda
José Luis García
JL
Jofré
Rosa
R
Menárguez
Javier
J
Cannata-Andía
Jorge
J
Cigudosa
Juan C
JC
D015415:Biomarkers; D002118:Calcium / Q000378:metabolism; D002869:Chromosome Aberrations; D004247:DNA / Q000235:genetics; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D017404:In Situ Hybridization, Fluorescence; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism; D016030:Kidney Transplantation; D010281:Parathyroid Hormone / Q000378:metabolism; D016105:Parathyroidectomy; D010710:Phosphates / Q000378:metabolism; D006435:Renal Dialysis
D015415:Biomarkers; D010281:Parathyroid Hormone; D010710:Phosphates; D004247:DNA; D002118:Calcium