Copy Number Variation in CCND1 Gene is Implicated in the Pathogenesis of Sporadic Parathyroid Carcinoma

Overview

Journal World J Surg

Publisher Wiley

Specialty General Surgery

Date 2014 Feb 11

PMID 24510244

Citations 16

Authors

Lin Zhao

Li-Hao Sun

Dong-Mei Liu

Xiao-Yan He

Bei Tao

Guang Ning

Jian-Min Liu

Hong-Yan Zhao

Affiliations

Soon will be listed here.

Abstract

Background: The molecular bases for parathyroid carcinomas present in conjunction with sporadic primary hyperparathyroidism are not fully elucidated. Gene copy number variations (CNVs) play an important role in tumorigenesis. The aim of the current study was to explore whether the CNVs of specific tumor-associated genes are involved in parathyroid carcinogenesis.

Methods: A multiplex ligation-dependent probe amplification method was used to compare differences in copy number in 39 common tumor-associated genes among 7 patients with parathyroid carcinoma and 14 age- and sex-matched subjects with parathyroid adenoma.

Results: It was shown that amplification of CCND1, a gene encoding cyclin D1, was more prevalent in parathyroid carcinomas than in adenomas (71 vs. 21 %, p = 0.056). This result was confirmed quantitatively by real-time polymerase chain reaction. Expression of CCND1 mRNA level was significantly higher in carcinomas than in adenomas (p = 0.003). Western blot and immunohistochemical analysis also demonstrated higher expression of CCND1 in carcinoma specimens than in adenoma samples.

Conclusions: It is thus inferred that gain in copy number of CCND1 is implicated in the molecular pathogenesis of parathyroid carcinoma.

Citing Articles

KMT2A and chronic inflammation as potential drivers of sporadic parathyroid adenoma.

Xu Q, La T, Ye K, Wang L, Wang S, Hu Y Clin Transl Med. 2024; 14(6):e1734.

PMID: 38888967 PMC: 11185127. DOI: 10.1002/ctm2.1734.

Cyclin-dependent kinases: Masters of the eukaryotic universe.

Pluta A, Studniarek C, Murphy S, Norbury C Wiley Interdiscip Rev RNA. 2023; :e1816.

PMID: 37718413 PMC: 10909489. DOI: 10.1002/wrna.1816.

A parathyroid cancer with soporous state, depression, and severe cognitive decline in acute renal failure.

Vultaggio F, Martino B, Nitro L, Fuccillo E, Felisati G, De Pasquale L Clin Case Rep. 2023; 11(7):e7627.

PMID: 37397577 PMC: 10310898. DOI: 10.1002/ccr3.7627.

Parathyroid carcinoma: molecular therapeutic targets.

Marini F, Giusti F, Palmini G, Aurilia C, Donati S, Brandi M Endocrine. 2023; 81(3):409-418.

PMID: 37160841 DOI: 10.1007/s12020-023-03376-w.

Molecular and Clinical Spectrum of Primary Hyperparathyroidism.

Jha S, Simonds W Endocr Rev. 2023; 44(5):779-818.

PMID: 36961765 PMC: 10502601. DOI: 10.1210/endrev/bnad009.

References

Vasef M, Brynes R, Sturm M, Bromley C, Robinson R . Expression of cyclin D1 in parathyroid carcinomas, adenomas, and hyperplasias: a paraffin immunohistochemical study. Mod Pathol. 1999; 12(4):412-6. View

Woodard G, Lin L, Zhang J, Agarwal S, Marx S, Simonds W . Parafibromin, product of the hyperparathyroidism-jaw tumor syndrome gene HRPT2, regulates cyclin D1/PRAD1 expression. Oncogene. 2004; 24(7):1272-6. DOI: 10.1038/sj.onc.1208274. View

Lee C, Iafrate A, Brothman A . Copy number variations and clinical cytogenetic diagnosis of constitutional disorders. Nat Genet. 2007; 39(7 Suppl):S48-54. DOI: 10.1038/ng2092. View

Tahara H, Smith A, Gas R, Cryns V, Arnold A . Genomic localization of novel candidate tumor suppressor gene loci in human parathyroid adenomas. Cancer Res. 1996; 56(3):599-605. View

Zahnleiter D, Uebe S, Ekici A, Hoyer J, Wiesener A, Wieczorek D . Rare copy number variants are a common cause of short stature. PLoS Genet. 2013; 9(3):e1003365. PMC: 3597495. DOI: 10.1371/journal.pgen.1003365. View

Hogervorst F, Nederlof P, Gille J, McElgunn C, Grippeling M, Pruntel R . Large genomic deletions and duplications in the BRCA1 gene identified by a novel quantitative method. Cancer Res. 2003; 63(7):1449-53. View

Veronese L, Tournilhac O, Combes P, Prie N, Pierre-Eymard E, Guieze R . Contribution of MLPA to routine diagnostic testing of recurrent genomic aberrations in chronic lymphocytic leukemia. Cancer Genet. 2013; 206(1-2):19-25. DOI: 10.1016/j.cancergen.2012.12.002. View

Reintjes N, Li Y, Becker A, Rohmann E, Schmutzler R, Wollnik B . Activating somatic FGFR2 mutations in breast cancer. PLoS One. 2013; 8(3):e60264. PMC: 3603931. DOI: 10.1371/journal.pone.0060264. View

Moelans C, Monsuur H, de Pinth J, Radersma R, de Weger R, van Diest P . ESR1 amplification is rare in breast cancer and is associated with high grade and high proliferation: a multiplex ligation-dependent probe amplification study. Cell Oncol (Dordr). 2011; 34(5):489-94. PMC: 3219866. DOI: 10.1007/s13402-011-0045-5. View

10.

Stuppia L, Antonucci I, Palka G, Gatta V . Use of the MLPA assay in the molecular diagnosis of gene copy number alterations in human genetic diseases. Int J Mol Sci. 2012; 13(3):3245-3276. PMC: 3317712. DOI: 10.3390/ijms13033245. View

11.

Eldering E, Spek C, Aberson H, Grummels A, Derks I, de Vos A . Expression profiling via novel multiplex assay allows rapid assessment of gene regulation in defined signalling pathways. Nucleic Acids Res. 2003; 31(23):e153. PMC: 290288. DOI: 10.1093/nar/gng153. View

12.

Agarwal S, Schrock E, Kester M, Burns A, Heffess C, Ried T . Comparative genomic hybridization analysis of human parathyroid tumors. Cancer Genet Cytogenet. 1998; 106(1):30-6. DOI: 10.1016/s0165-4608(98)00049-1. View

13.

Bergero N, De Pompa R, Sacerdote C, Gasparri G, Volante M, Bussolati G . Galectin-3 expression in parathyroid carcinoma: immunohistochemical study of 26 cases. Hum Pathol. 2005; 36(8):908-14. DOI: 10.1016/j.humpath.2005.06.020. View

14.

Rogers A, Chu J, Darvishi K, Ionita-Laza I, Lehmann H, Mills R . Copy number variation prevalence in known asthma genes and their impact on asthma susceptibility. Clin Exp Allergy. 2013; 43(4):455-62. PMC: 3609036. DOI: 10.1111/cea.12060. View

15.

Newey P, Nesbit M, Rimmer A, Attar M, Head R, Christie P . Whole-exome sequencing studies of nonhereditary (sporadic) parathyroid adenomas. J Clin Endocrinol Metab. 2012; 97(10):E1995-2005. PMC: 4446457. DOI: 10.1210/jc.2012-2303. View

16.

Cromer M, Starker L, Choi M, Udelsman R, Nelson-Williams C, Lifton R . Identification of somatic mutations in parathyroid tumors using whole-exome sequencing. J Clin Endocrinol Metab. 2012; 97(9):E1774-81. PMC: 5393442. DOI: 10.1210/jc.2012-1743. View

17.

Shane E . Clinical review 122: Parathyroid carcinoma. J Clin Endocrinol Metab. 2001; 86(2):485-93. DOI: 10.1210/jcem.86.2.7207. View

18.

Hess C, Denkers F, Ossenkoppele G, Waisfisz Q, McElgunn C, Eldering E . Gene expression profiling of minimal residual disease in acute myeloid leukaemia by novel multiplex-PCR-based method. Leukemia. 2004; 18(12):1981-8. DOI: 10.1038/sj.leu.2403520. View

19.

Schouten J, McElgunn C, Waaijer R, Zwijnenburg D, Diepvens F, Pals G . Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res. 2002; 30(12):e57. PMC: 117299. DOI: 10.1093/nar/gnf056. View

20.

Bricaire L, Odou M, Cardot-Bauters C, Delemer B, North M, Salenave S . Frequent large germline HRPT2 deletions in a French National cohort of patients with primary hyperparathyroidism. J Clin Endocrinol Metab. 2013; 98(2):E403-8. DOI: 10.1210/jc.2012-2789. View