Intragenic allelic loss and promoter hypermethylation of the RIZ1 tumor suppressor gene in parathyroid tumors and pheochromocytomas
(2003) In Surgery 134(6). p.9-932- Abstract
BACKGROUND: Loss of heterozygosity (LOH) at chromosome 1p is a common abnormality in both parathyroid tumors and pheochromocytomas. The recently characterized tumor suppressor gene RIZ1, located at 1p36, has emerged as a putative candidate to be involved in endocrine tumorigenesis.
MATERIAL: Presence of allelic loss, promoter hypermethylation, and mutational aberrations of the RIZ1 gene were investigated using PCR-based techniques in 47 parathyroid tumors and 23 pheochromocytomas. Gene expression studies used the RNAse protection assay.
RESULTS: RIZ1 mRNA is expressed in pathologic tissues of the parathyroid and adrenal medulla. Thirteen of 47 (28%) parathyroid tumors, and 9/23 (39%) pheochromocytomas displayed LOH within... (More)
BACKGROUND: Loss of heterozygosity (LOH) at chromosome 1p is a common abnormality in both parathyroid tumors and pheochromocytomas. The recently characterized tumor suppressor gene RIZ1, located at 1p36, has emerged as a putative candidate to be involved in endocrine tumorigenesis.
MATERIAL: Presence of allelic loss, promoter hypermethylation, and mutational aberrations of the RIZ1 gene were investigated using PCR-based techniques in 47 parathyroid tumors and 23 pheochromocytomas. Gene expression studies used the RNAse protection assay.
RESULTS: RIZ1 mRNA is expressed in pathologic tissues of the parathyroid and adrenal medulla. Thirteen of 47 (28%) parathyroid tumors, and 9/23 (39%) pheochromocytomas displayed LOH within the RIZ1 gene locus. Promoter hypermethylation of RIZ1 was detected in 36% of the parathyroid tumors and was related to LOH at the RIZ1 locus (P=.01), and absence of somatic mutation of the MEN1 gene (P=.044). In the pheochromocytomas, none of the benign tumors, but 2/4 malignant specimens exhibited RIZ1 promoter hypermethylation.
CONCLUSION: Alteration of the RIZ1 gene locus via intragenic allelic loss and promoter hypermethylation seem common in parathyroid tumors. Inactivation of the RIZ1 gene may cause parathyroid tumorigenesis via a mechanism in which genetic alteration of the MEN1 gene is redundant.
(Less)
- author
- Carling, Tobias ; Du, Yong ; Fang, Wei ; Correa, Pamela LU and Huang, Shi
- publishing date
- 2003
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adolescent, Adrenal Gland Neoplasms/genetics, Adult, Aged, Aged, 80 and over, Cell Transformation, Neoplastic/genetics, DNA Methylation, DNA-Binding Proteins/genetics, Female, Gene Expression/genetics, Genes, Tumor Suppressor/physiology, Histone-Lysine N-Methyltransferase, Humans, Loss of Heterozygosity/genetics, Male, Middle Aged, Nuclear Proteins/genetics, Parathyroid Neoplasms/genetics, Pheochromocytoma/genetics, Promoter Regions, Genetic/genetics, Transcription Factors/genetics
- in
- Surgery
- volume
- 134
- issue
- 6
- pages
- 9 - 932
- publisher
- Elsevier
- external identifiers
-
- pmid:14668725
- scopus:0347517693
- ISSN
- 0039-6060
- DOI
- 10.1016/s0039-6060(03)00422-7
- language
- English
- LU publication?
- no
- id
- b9ce7271-1015-4dad-ace0-5993884f3a27
- date added to LUP
- 2021-11-29 10:54:07
- date last changed
- 2024-01-20 18:29:48
@article{b9ce7271-1015-4dad-ace0-5993884f3a27,
abstract = {{<p>BACKGROUND: Loss of heterozygosity (LOH) at chromosome 1p is a common abnormality in both parathyroid tumors and pheochromocytomas. The recently characterized tumor suppressor gene RIZ1, located at 1p36, has emerged as a putative candidate to be involved in endocrine tumorigenesis.</p><p>MATERIAL: Presence of allelic loss, promoter hypermethylation, and mutational aberrations of the RIZ1 gene were investigated using PCR-based techniques in 47 parathyroid tumors and 23 pheochromocytomas. Gene expression studies used the RNAse protection assay.</p><p>RESULTS: RIZ1 mRNA is expressed in pathologic tissues of the parathyroid and adrenal medulla. Thirteen of 47 (28%) parathyroid tumors, and 9/23 (39%) pheochromocytomas displayed LOH within the RIZ1 gene locus. Promoter hypermethylation of RIZ1 was detected in 36% of the parathyroid tumors and was related to LOH at the RIZ1 locus (P=.01), and absence of somatic mutation of the MEN1 gene (P=.044). In the pheochromocytomas, none of the benign tumors, but 2/4 malignant specimens exhibited RIZ1 promoter hypermethylation.</p><p>CONCLUSION: Alteration of the RIZ1 gene locus via intragenic allelic loss and promoter hypermethylation seem common in parathyroid tumors. Inactivation of the RIZ1 gene may cause parathyroid tumorigenesis via a mechanism in which genetic alteration of the MEN1 gene is redundant.</p>}},
author = {{Carling, Tobias and Du, Yong and Fang, Wei and Correa, Pamela and Huang, Shi}},
issn = {{0039-6060}},
keywords = {{Adolescent; Adrenal Gland Neoplasms/genetics; Adult; Aged; Aged, 80 and over; Cell Transformation, Neoplastic/genetics; DNA Methylation; DNA-Binding Proteins/genetics; Female; Gene Expression/genetics; Genes, Tumor Suppressor/physiology; Histone-Lysine N-Methyltransferase; Humans; Loss of Heterozygosity/genetics; Male; Middle Aged; Nuclear Proteins/genetics; Parathyroid Neoplasms/genetics; Pheochromocytoma/genetics; Promoter Regions, Genetic/genetics; Transcription Factors/genetics}},
language = {{eng}},
number = {{6}},
pages = {{9--932}},
publisher = {{Elsevier}},
series = {{Surgery}},
title = {{Intragenic allelic loss and promoter hypermethylation of the RIZ1 tumor suppressor gene in parathyroid tumors and pheochromocytomas}},
url = {{http://dx.doi.org/10.1016/s0039-6060(03)00422-7}},
doi = {{10.1016/s0039-6060(03)00422-7}},
volume = {{134}},
year = {{2003}},
}