title: Upregulation of FGFR1 expression is associated with parathyroid carcinogenesis in HPT-JT syndrome due to an HRPT2 splicing mutation.
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.
authors.affiliation: 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.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Eun-Yeong
authors.initials: EY
authors.lastname: Mo
authors.affiliation: 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.
authors.forename: Eun-Sook
authors.initials: ES
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Je-Ho
authors.initials: JH
authors.lastname: Han
authors.affiliation: Department of Hospital Pathology, Incheon St. Mary's Hospital, The Catholic University of Korea, Bupyeong-gu, Incheon 403-720, Republic of Korea.
authors.forename: Lee-So
authors.initials: LS
authors.lastname: Maeng
authors.affiliation: Department of Hospital Pathology, Incheon St. Mary's Hospital, The Catholic University of Korea, Bupyeong-gu, Incheon 403-720, Republic of Korea.
authors.forename: An-Hee
authors.initials: AH
authors.lastname: Lee
authors.affiliation: Department of Pathology, Microdissection Genomics Research Center, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul 137-701, Republic of Korea.
authors.forename: Jung Woo
authors.initials: JW
authors.lastname: Eun
authors.affiliation: Department of Pathology, Microdissection Genomics Research Center, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul 137-701, Republic of Korea.
authors.forename: Suk Woo
authors.initials: SW
authors.lastname: Nam
authors.affiliation: 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.
authors.forename: Sung-Dae
authors.initials: SD
authors.lastname: Moon
mesh_terms: D000236:Adenoma / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism*; D016000:Cluster Analysis; D005260:Female; D005350:Fibroma / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006961:Hyperparathyroidism / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D007573:Jaw Neoplasms / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010282:Parathyroid Neoplasms / Q000235:genetics / Q000378:metabolism*; D012326:RNA Splicing; D060888:Real-Time Polymerase Chain Reaction; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C454900:CDC73 protein, human; D025521:Tumor Suppressor Proteins; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1