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Published on: August 23, 2019
The status of CDKN2A alpha (p16INK4A) and beta (p14ARF) transcripts in thyroid tumour progression
A Ferru1, G Fromont, H Gibelin
1Laboratoire d'Oncologie Moléculaire EA3805, PBS, Cité Hospitalière de la Milétrie, Avenue du Recteur Pineau 86021, Poitiers, France.
Abstract:
CDKN2A locus on chromosome 9p21 encodes two tumour suppressor proteins pl6INK4A, which is a regulator of the retinoblastoma (RB) protein, and p14ARF, which is involved in the ARF-Mdm2-p53 pathway. The aim of this study was to determine if CDKN2A gene products are implicated in differentiated thyroid carcinogenesis and progression. We used real-time quantitative RT-PCR and immunohistochemistry to assess both transcripts and proteins levels in 60 tumours specimens. Overexpression of p14ARF and pl6INK4A was observed in follicular adenomas, follicular carcinomas and papillary carcinomas, while downregulation was found in oncocytic adenomas compared to nontumoral paired thyroid tissues. These deregulations were statistically significant for pl6INK4a (P=0.006) in follicular adenomas and close to statistical significance for p14ARF in follicular adenomas (P=0.06) and in papillary carcinomas (P=0.05). In all histological types, except papillary carcinomas, we observed a statistically significant relationship between p14ARF and E2F1 (r=0.64 to 1, P<0.05). Our data are consistent with involvement of CDKN2A transcript upregulation in thyroid follicular tumorigenesis as an early event. However, these deregulations do not appear to be correlated to the clinical outcome and they could not be used as potential prognostic markers.
Insights
The CDKN2A gene
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The CDKN2A gene locus on chromosome 9p21 encodes tumor suppressor proteins p16INK4A and p14ARF.
- These proteins regulate key cellular pathways, including the retinoblastoma (RB) protein pathway and the ARF-Mdm2-p53 pathway.
- Dysregulation of tumor suppressor genes is implicated in various cancers, including thyroid cancer.
Purpose of the Study:
- To investigate the role of CDKN2A gene products (p16INK4A and p14ARF) in the development and progression of differentiated thyroid cancer.
- To assess the expression levels of CDKN2A transcripts and proteins in different types of thyroid tumors.
Main Methods:
- Real-time quantitative RT-PCR was used to measure transcript levels.
- Immunohistochemistry was employed to assess protein expression.
- Sixty thyroid tumor specimens were analyzed and compared to non-tumoral thyroid tissues.
Main Results:
- Overexpression of p14ARF and p16INK4A was observed in follicular adenomas, follicular carcinomas, and papillary carcinomas.
- Downregulation of these proteins was noted in oncocytic adenomas compared to normal thyroid tissue.
- Statistically significant deregulation of p16INK4A was found in follicular adenomas (P=0.006).
- A significant relationship between p14ARF and E2F1 was observed in most histological types (r=0.64 to 1, P<0.05).
Conclusions:
- CDKN2A transcript upregulation appears to be an early event in thyroid follicular tumorigenesis.
- Observed deregulations in CDKN2A gene products are not correlated with clinical outcomes.
- These findings suggest that CDKN2A alterations may not serve as prognostic markers for differentiated thyroid cancer.
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