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CCND1 Splice Variant as A Novel Diagnostic and Predictive Biomarker for Thyroid Cancer

1,2,3, 1,2,3, 1,2,3, 3,4 and 1,2,3,*
1
Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
2
Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul 06591, Korea
3
Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
4
Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
*
Author to whom correspondence should be addressed.
Cancers 2018, 10(11), 437; https://doi.org/10.3390/cancers10110437
Received: 20 October 2018 / Revised: 11 November 2018 / Accepted: 12 November 2018 / Published: 13 November 2018
(This article belongs to the Special Issue Thyroid Cancer)
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PDF [3560 KB, uploaded 13 November 2018]
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Abstract

Cyclin D1 protein is aberrantly overexpressed in thyroid cancers, but mutations of the CCND1 gene are rare in these tumors. We investigated the CCND1 rs9344 (G870A) polymorphism and the expression profiles of wild-type CCND1a and shortened oncogenic isoform CCND1b at the mRNA and protein levels in 286 thyroid tumors. Genotype AA of rs9344 was associated with high expression of CCND1b mRNA and was more frequently found in thyroid cancer than in benign tumors. The mRNA expression levels of CCND1b were higher in papillary thyroid carcinoma (PTC) than in benign or other malignant tumors. However, the expression of CCND1a mRNA showed no association with the parameters. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was distinguished from PTC by low expression of CCND1b at mRNA and protein levels. We further observed that cyclin D1b immunostaining helped to avoid the misdiagnosis of classic PTC with predominant follicular pattern as NIFTP in a separate cohort. Nuclear cyclin D1b expression was associated with aggressive clinicopathologic features in PTC. These findings suggest that cyclin D1b overexpression can be used as a diagnostic and predictive biomarker in thyroid tumors and may be functionally involved in the development and progression of the disease. View Full-Text
Keywords: CCND1; cyclin D1; CCND1b; cyclin D1b; thyroid cancer; papillary thyroid carcinoma; noninvasive follicular thyroid neoplasm with papillary-like nuclear features; NIFTP; BRAF; polymorphism CCND1; cyclin D1; CCND1b; cyclin D1b; thyroid cancer; papillary thyroid carcinoma; noninvasive follicular thyroid neoplasm with papillary-like nuclear features; NIFTP; BRAF; polymorphism
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Jeon, S.; Kim, Y.; Jeong, Y.M.; Bae, J.S.; Jung, C.K. CCND1 Splice Variant as A Novel Diagnostic and Predictive Biomarker for Thyroid Cancer. Cancers 2018, 10, 437.

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