Genomic and transcriptomic profiling reveal molecular characteristics of parathyroid carcinoma

被引:7
|
作者
Jo, Se-Young [1 ,2 ]
Hong, Namki [3 ]
Lee, Seunghyun [3 ,4 ]
Jeong, Jong Ju [5 ]
Won, Jeongsoo [1 ,2 ]
Park, Jiho [1 ]
Kim, Gi Jeong [6 ]
Kim, Sang Kyum [6 ]
Kim, Sangwoo [1 ,2 ,7 ]
Rhee, Yumie [3 ]
机构
[1] Yonsei Univ, Coll Med, Dept Biomed Syst Informat, Seoul, South Korea
[2] Yonsei Univ, Coll Med, Brain Korea PLUS Project Med Sci 21, Seoul, South Korea
[3] Yonsei Univ, Severance Hosp, Coll Med, Endocrine Res Inst,Dept Internal Med, Seoul, South Korea
[4] Yonsei Univ, Wonju Severance Christian Hosp, Wonju Coll Med, Dept Internal Med, Wonju, South Korea
[5] Yonsei Univ, Severance Hosp, Coll Med, Dept Surg, Seoul, South Korea
[6] Yonsei Univ, Coll Med, Dept Pathol, Seoul, South Korea
[7] Pohang Univ Sci & Technol POSTECH, Postech Biotech Ctr, Pohang, South Korea
来源
EXPERIMENTAL AND MOLECULAR MEDICINE | 2023年 / 55卷 / 05期
关键词
GENE-EXPRESSION; CELL-PROLIFERATION; COPY NUMBER; CANCER; CDC73; MUTATIONS; PARAFIBROMIN; WT1; MUTAGENESIS; REPRESSION;
D O I
10.1038/s12276-023-00968-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Genomic and transcriptomic profiling has enhanced the diagnostic and treatment options for many cancers. However, the molecular characteristics of parathyroid cancer remain largely unexplored, thereby limiting the development of new therapeutic interventions. Herein, we conducted genomic and transcriptomic sequencing of 50 parathyroid tissues (12 carcinomas, 28 adenomas, and 10 normal tissues) to investigate the intrinsic and comparative molecular features of parathyroid carcinoma. We confirmed multiple two-hit mutation patterns in cell division cycle 73 (CDC73) that converged to biallelic inactivation, calling into question the presence of a second hit in other genes. In addition, allele-specific repression of CDC73 in copies with germline-truncating variants suggested selective pressure prior to tumorigenesis. Transcriptomic analysis identified upregulation of the expression of E2F targets, KRAS and TNF-alpha signaling, and epithelial-mesenchymal transition pathways in carcinomas compared to adenomas and normal tissues. A molecular classification model based on carcinoma-specific genes clearly separated carcinomas from adenomas and normal tissues, the clinical utility of which was demonstrated in two patients with uncertain malignant potential. A deeper analysis of gene expression and functional prediction suggested that Wilms tumor 1 (WT1) is a potential biomarker for CDC73-mutant parathyroid carcinoma, which was further validated through immunohistochemistry. Overall, our study revealed the genomic and transcriptomic profiles of parathyroid carcinoma and may help direct future precision diagnostic and therapeutic improvements.
引用
收藏
页码:886 / 897
页数:12
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