Genomic and transcriptomic profiling reveal molecular characteristics of parathyroid carcinoma
Abstract 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 an...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-05-01
|
| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-023-00968-4 |
| _version_ | 1797811960721440768 |
|---|---|
| author | Se-Young Jo Namki Hong Seunghyun Lee Jong Ju Jeong Jeongsoo Won Jiho Park Gi Jeong Kim Sang Kyum Kim Sangwoo Kim Yumie Rhee |
| author_facet | Se-Young Jo Namki Hong Seunghyun Lee Jong Ju Jeong Jeongsoo Won Jiho Park Gi Jeong Kim Sang Kyum Kim Sangwoo Kim Yumie Rhee |
| author_sort | Se-Young Jo |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-13T07:30:30Z |
| format | Article |
| id | doaj.art-64f236f6f6484f1290b950293f5d1594 |
| institution | Directory Open Access Journal |
| issn | 2092-6413 |
| language | English |
| last_indexed | 2024-03-13T07:30:30Z |
| publishDate | 2023-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj.art-64f236f6f6484f1290b950293f5d15942023-06-04T11:07:24ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132023-05-0155588689710.1038/s12276-023-00968-4Genomic and transcriptomic profiling reveal molecular characteristics of parathyroid carcinomaSe-Young Jo0Namki Hong1Seunghyun Lee2Jong Ju Jeong3Jeongsoo Won4Jiho Park5Gi Jeong Kim6Sang Kyum Kim7Sangwoo Kim8Yumie Rhee9Department of Biomedical Systems Informatics, Yonsei University College of MedicineDepartment of Internal Medicine, Severance Hospital, Endocrine Research Institute, Yonsei University College of MedicineDepartment of Internal Medicine, Severance Hospital, Endocrine Research Institute, Yonsei University College of MedicineDepartment of Surgery, Severance Hospital, Yonsei University College of MedicineDepartment of Biomedical Systems Informatics, Yonsei University College of MedicineDepartment of Biomedical Systems Informatics, Yonsei University College of MedicineDepartment of Pathology, Yonsei University College of MedicineDepartment of Pathology, Yonsei University College of MedicineDepartment of Biomedical Systems Informatics, Yonsei University College of MedicineDepartment of Internal Medicine, Severance Hospital, Endocrine Research Institute, Yonsei University College of MedicineAbstract 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.https://doi.org/10.1038/s12276-023-00968-4 |
| spellingShingle | Se-Young Jo Namki Hong Seunghyun Lee Jong Ju Jeong Jeongsoo Won Jiho Park Gi Jeong Kim Sang Kyum Kim Sangwoo Kim Yumie Rhee Genomic and transcriptomic profiling reveal molecular characteristics of parathyroid carcinoma Experimental and Molecular Medicine |
| title | Genomic and transcriptomic profiling reveal molecular characteristics of parathyroid carcinoma |
| title_full | Genomic and transcriptomic profiling reveal molecular characteristics of parathyroid carcinoma |
| title_fullStr | Genomic and transcriptomic profiling reveal molecular characteristics of parathyroid carcinoma |
| title_full_unstemmed | Genomic and transcriptomic profiling reveal molecular characteristics of parathyroid carcinoma |
| title_short | Genomic and transcriptomic profiling reveal molecular characteristics of parathyroid carcinoma |
| title_sort | genomic and transcriptomic profiling reveal molecular characteristics of parathyroid carcinoma |
| url | https://doi.org/10.1038/s12276-023-00968-4 |
| work_keys_str_mv | AT seyoungjo genomicandtranscriptomicprofilingrevealmolecularcharacteristicsofparathyroidcarcinoma AT namkihong genomicandtranscriptomicprofilingrevealmolecularcharacteristicsofparathyroidcarcinoma AT seunghyunlee genomicandtranscriptomicprofilingrevealmolecularcharacteristicsofparathyroidcarcinoma AT jongjujeong genomicandtranscriptomicprofilingrevealmolecularcharacteristicsofparathyroidcarcinoma AT jeongsoowon genomicandtranscriptomicprofilingrevealmolecularcharacteristicsofparathyroidcarcinoma AT jihopark genomicandtranscriptomicprofilingrevealmolecularcharacteristicsofparathyroidcarcinoma AT gijeongkim genomicandtranscriptomicprofilingrevealmolecularcharacteristicsofparathyroidcarcinoma AT sangkyumkim genomicandtranscriptomicprofilingrevealmolecularcharacteristicsofparathyroidcarcinoma AT sangwookim genomicandtranscriptomicprofilingrevealmolecularcharacteristicsofparathyroidcarcinoma AT yumierhee genomicandtranscriptomicprofilingrevealmolecularcharacteristicsofparathyroidcarcinoma |