Open AccessUpregulation of FGFR1 expression is associated with parathyroid carcinogenesis in HPT-JT syndrome due to an HRPT2 splicing mutation
Author(s) -
Jiyoung Lee,
Su Yeon Kim,
Eun-Yeong Mo,
Eun-Sook Kim,
Je-Ho Han,
Lee-So Maeng,
An-Hee Lee,
Jung Woo Eun,
Suk Woo Nam,
Sung Dae Moon
Publication year - 2014
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2014.2477
Subject(s) - parathyroid adenoma , parathyroid carcinoma , biology , adenoma , cancer research , carcinogenesis , exon , primary hyperparathyroidism , alternative splicing , parathyroid neoplasm , pathology , endocrinology , cancer , gene , medicine , genetics
Mutations of the HRPT2 gene, which are responsible for hyperparathyroidism-jaw tumor (HPT-JT) syndrome, have been implicated in the development of a high proportion of parathyroid carcinomas. The aim of this study was to investigate differences in expression of the most important genes connected with parathyroid carcinoma between HPT-JT syndrome due to an HRPT2 splicing mutation, normal parathyroid tissue and sporadic parathyroid adenoma. Total RNAs were extracted from parathyroid carcinoma in HPT-JT syndrome harbouring HRPT2 splicing mutation or sporadic parathyroid adenoma and normal parathyroid gland, and subjected to Illumina DASL-based gene expression assay. Unsupervised hierarchical clustering analysis was used to compare gene expression in HPT-JT syndrome, sporadic parathyroid adenoma and normal parathyroid glands. We identified differentially regulated genes in HPT-JT syndrome and sporadic parathyroid adenoma relative to normal parathyroid glands using a combination of Welch's t-test and fold-change analysis. Quantitative PCR, RT-PCR and IHC were used for validation. Sixteen genes differentially regulated in the parathyroid carcinoma were associated with signal pathways, MAPK, regulation of actin cytoskeleton, prostate cancer and apoptosis. FGFR1 expression was confirmed to be significantly upregulated by validation experiments. Our gene expression profiling experiments suggest that upregulated FGFR1 expression appears to be associated with parathyroid carcinoma in HPT-JT syndrome due to an HRPT2 splicing mutation.