Genome-wide and locus specific alterations in CDC73/HRPT2-mutated parathyroid tumors.

Mutations in the hyperparathyroidism type 2 (HRPT2/CDC73) gene and alterations in the parafibromin protein have been established in the majority of parathyroid carcinomas and in subsets of parathyroid adenomas. While it is known that CDC73-mutated parathyroid tumors display specific gene expression...

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Autores principales:	Luqman Sulaiman, Felix Haglund, Jamileh Hashemi, Takao Obara, Jörgen Nordenström, Catharina Larsson, C Christofer Juhlin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/506d7ad0a0ef4f85861e4be472e3ad0c
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spelling	oai:doaj.org-article:506d7ad0a0ef4f85861e4be472e3ad0c2021-11-18T08:13:41ZGenome-wide and locus specific alterations in CDC73/HRPT2-mutated parathyroid tumors.1932-620310.1371/journal.pone.0046325https://doaj.org/article/506d7ad0a0ef4f85861e4be472e3ad0c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23029479/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Mutations in the hyperparathyroidism type 2 (HRPT2/CDC73) gene and alterations in the parafibromin protein have been established in the majority of parathyroid carcinomas and in subsets of parathyroid adenomas. While it is known that CDC73-mutated parathyroid tumors display specific gene expression changes compared to CDC73 wild-type cases, the molecular cytogenetic profile in CDC73-mutated cases compared to unselected adenomas (with an expected very low frequency of CDC73 mutations) remains unknown. For this purpose, nine parathyroid tumors with established CDC73 gene inactivating mutations (three carcinomas, one atypical adenoma and five adenomas) were analyzed for copy number alterations and loss of heterozygosity using array-comparative genomic hybridization (a-CGH) and single nucleotide polymorphism (SNP) microarrays, respectively. Furthermore, CDC73 gene promoter methylation levels were assessed using bisulfite Pyrosequencing. The panel included seven tumors with single mutation and three with double mutations of the CDC73 gene. The carcinomas displayed copy number alterations in agreement with previous studies, whereas the CDC73-mutated adenomas did not display the same pattern of alterations at loci frequently deleted in unselected parathyroid tumors. Furthermore, gross losses of chromosomal material at 1p and 13 were significantly (p = 0.012) associated with parathyroid carcinomas as opposed to adenomas. Quantitative PCR-based copy number loss regarding CDC73 was observed in three adenomas, while all the carcinomas were diploid or showed copy number gain for CDC73 gene. Hypermethylation of the CDC73 gene promoter was not observed. Our data could suggest that CDC73-mutated parathyroid adenomas exhibit a partly unique cytogenetic profile in addition to that of carcinomas and unselected adenomas. Furthermore, CDC73-mutated carcinomas displayed losses at 1p and 13 which are not seen in CDC73-mutated adenomas, making these regions of interest for further studies regarding malignant properties in tumors from CDC73-mutated cases. However, due to the small sample size, validation of the results in a larger cohort is warranted.Luqman SulaimanFelix HaglundJamileh HashemiTakao ObaraJörgen NordenströmCatharina LarssonC Christofer JuhlinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e46325 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Luqman Sulaiman Felix Haglund Jamileh Hashemi Takao Obara Jörgen Nordenström Catharina Larsson C Christofer Juhlin Genome-wide and locus specific alterations in CDC73/HRPT2-mutated parathyroid tumors.
description	Mutations in the hyperparathyroidism type 2 (HRPT2/CDC73) gene and alterations in the parafibromin protein have been established in the majority of parathyroid carcinomas and in subsets of parathyroid adenomas. While it is known that CDC73-mutated parathyroid tumors display specific gene expression changes compared to CDC73 wild-type cases, the molecular cytogenetic profile in CDC73-mutated cases compared to unselected adenomas (with an expected very low frequency of CDC73 mutations) remains unknown. For this purpose, nine parathyroid tumors with established CDC73 gene inactivating mutations (three carcinomas, one atypical adenoma and five adenomas) were analyzed for copy number alterations and loss of heterozygosity using array-comparative genomic hybridization (a-CGH) and single nucleotide polymorphism (SNP) microarrays, respectively. Furthermore, CDC73 gene promoter methylation levels were assessed using bisulfite Pyrosequencing. The panel included seven tumors with single mutation and three with double mutations of the CDC73 gene. The carcinomas displayed copy number alterations in agreement with previous studies, whereas the CDC73-mutated adenomas did not display the same pattern of alterations at loci frequently deleted in unselected parathyroid tumors. Furthermore, gross losses of chromosomal material at 1p and 13 were significantly (p = 0.012) associated with parathyroid carcinomas as opposed to adenomas. Quantitative PCR-based copy number loss regarding CDC73 was observed in three adenomas, while all the carcinomas were diploid or showed copy number gain for CDC73 gene. Hypermethylation of the CDC73 gene promoter was not observed. Our data could suggest that CDC73-mutated parathyroid adenomas exhibit a partly unique cytogenetic profile in addition to that of carcinomas and unselected adenomas. Furthermore, CDC73-mutated carcinomas displayed losses at 1p and 13 which are not seen in CDC73-mutated adenomas, making these regions of interest for further studies regarding malignant properties in tumors from CDC73-mutated cases. However, due to the small sample size, validation of the results in a larger cohort is warranted.
format	article
author	Luqman Sulaiman Felix Haglund Jamileh Hashemi Takao Obara Jörgen Nordenström Catharina Larsson C Christofer Juhlin
author_facet	Luqman Sulaiman Felix Haglund Jamileh Hashemi Takao Obara Jörgen Nordenström Catharina Larsson C Christofer Juhlin
author_sort	Luqman Sulaiman
title	Genome-wide and locus specific alterations in CDC73/HRPT2-mutated parathyroid tumors.
title_short	Genome-wide and locus specific alterations in CDC73/HRPT2-mutated parathyroid tumors.
title_full	Genome-wide and locus specific alterations in CDC73/HRPT2-mutated parathyroid tumors.
title_fullStr	Genome-wide and locus specific alterations in CDC73/HRPT2-mutated parathyroid tumors.
title_full_unstemmed	Genome-wide and locus specific alterations in CDC73/HRPT2-mutated parathyroid tumors.
title_sort	genome-wide and locus specific alterations in cdc73/hrpt2-mutated parathyroid tumors.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/506d7ad0a0ef4f85861e4be472e3ad0c
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Genome-wide and locus specific alterations in CDC73/HRPT2-mutated parathyroid tumors.

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