Upregulation of FGFR1 expression is associated with parathyroid carcinogenesis in HPT-JT syndrome due to an HRPT2 splicing mutation

Lee,Ji-Young; Kim,Su  Yeon; Mo,Eun-Yeong; Kim,Eun-Sook; Han,Je-Ho; Maeng,Lee-So; Lee,An-Hee; Eun,Jung  Woo; Nam,Suk  Woo; Moon,Sung-Dae

doi:10.3892/ijo.2014.2477

Upregulation of FGFR1 expression is associated with parathyroid carcinogenesis in HPT-JT syndrome due to an HRPT2 splicing mutation

Authors:
- Ji-Young 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
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Affiliations: Division of Endocrinology and Metabolism, Department of Internal Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, Bupyeong-gu, Incheon 403-720, Republic of Korea, Department of Hospital Pathology, Incheon St. Mary's Hospital, The Catholic University of Korea, Bupyeong-gu, Incheon 403-720, Republic of Korea, Department of Pathology, Microdissection Genomics Research Center, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul 137-701, Republic of Korea
Published online on: May 29, 2014 https://doi.org/10.3892/ijo.2014.2477
Pages: 641-650

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Abstract

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.

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