The status of CDKN2A alpha (p16INK4A) and beta (p14ARF) transcripts in thyroid tumour progression

Ferru, Aurélie; Fromont, Gaëlle; Gibelin, Hélène; Guilhot, Joëlle; Savagner, Frédérique; Tourani, Jean-Marc; Kraimps, J. L.; Larsen, Christian‐Jacques; Karayan‐Tapon, Lucie

doi:10.1038/sj.bjc.6603479

Cited by 39 publications

(34 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…INK4a in adenomas, papillary and follicular tumours, and the loss of expression in ATC was observed in previous works (Ferru et al 2006, Ball et al 2007, suggesting that p16…”

Section: Ink4amentioning

confidence: 88%

Evidence of oncogene-induced senescence in thyroid carcinogenesis

Vizioli

Possik

Tarantino

et al. 2011

Endocrine-Related Cancer

View full text Add to dashboard Cite

Oncogene-induced senescence (OIS) is a growth arrest triggered by the enforced expression of cancer-promoting genes and acts as a barrier against malignant transformation in vivo. In this study, by a combination of in vitro and in vivo approaches, we investigate the role of OIS in tumours originating from the thyroid epithelium. We found that expression of different thyroid tumour-associated oncogenes in primary human thyrocytes triggers senescence, as demonstrated by the presence of OIS hallmarks: changes in cell morphology, accumulation of SA-b-Gal and senescence-associated heterochromatic foci, and upregulation of transcription of the cyclindependent kinase inhibitors p16INK4a and p21 CIP1 . Furthermore, immunohistochemical analysis of a panel of thyroid tumours characterised by different aggressiveness showed that the expression of OIS markers such as p16 INK4a, p21 CIP1 and IGFBP7 is upregulated at early stages, and lost during thyroid tumour progression. Taken together, our results suggest a role of OIS in thyroid carcinogenesis.

show abstract

“…INK4a in adenomas, papillary and follicular tumours, and the loss of expression in ATC was observed in previous works (Ferru et al 2006, Ball et al 2007, suggesting that p16…”

Section: Ink4amentioning

confidence: 88%

Evidence of oncogene-induced senescence in thyroid carcinogenesis

Vizioli

Possik

Tarantino

et al. 2011

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…In this regard, it is interesting to note that P16INK4a overexpression was significantly higher in MDM2+/CDK4+ WDLPS/DDLPS than in MDM2+/CDK4-WDLPS/DDLPS. P16INK4a overexpression has been reported in several tumor types such as gliomas (26), myxoid liposarcomas (27), thyroid carcinomas (28), and cervical carcinomas (29). P16INK4a overexpression might be a secondary event to RB1 inactivation, because RB1 repressed P16INK4a at the transcriptional level (30,31).…”

Section: Discussionmentioning

confidence: 99%

Clinical and Biological Significance of CDK4 Amplification in Well-Differentiated and Dedifferentiated Liposarcomas

Italiano

Bianchini

Gjernes

et al. 2009

Clinical Cancer Research

125

View full text Add to dashboard Cite

Purpose: The MDM2 and HMGA2 genes are consistently amplified in well-differentiated/ dedifferentiated liposarcomas (WDLPS/DDLPS) whereas CDK4 is frequently but not always amplified in these tumors. Our goal was to determine whether the absence of CDK4 amplification was (a) correlated to a specific clinico-histopathologic profile; and (b) compensated by another genomic anomaly involving the CCND1/CDK4/P16INK4a/ RB1/E2F pathway. Experimental Design: We compared the clinical characteristics of a series of 143 WDLPS/ DDLPS with amplification of both MDM2 and CDK4 (MDM2+/CDK4+) to a series of 45 WDLPS/DDLPS with MDM2 amplification and no CDK4 amplification (MDM2+/CDK4-). We used fluorescence in situ hybridization, real time quantitative reverse transcription PCR, and immunohistochemistry to explore the status of CCND1, P16INK4a, P14ARF, and RB1. Results: We found that MDM2+/CDK4-WDLPS/DDLPS represent a distinct clinical subgroup with favorable prognostic features, including low-grade lipoma-like histology, peripheral location, and lower rate of recurrence. By using fluorescence in situ hybridization, we found that genomic aberrations expected to be alternative mechanisms for compensating the lack of CDK4 amplification, such as RB1 and CDKN2A deletions or CCND1 amplification, were very uncommon. In contrast, by using real time quantitative reverse transcription PCR and immunohistochemistry, we observed that overexpression of P16INK4a (and P14ARF) and CCND1 and reduced expression of RB1 were very frequent, independently of the CDK4 status. Conclusions: Our results underscore the complex coordinated regulation of the RB and p53 growth-control pathways in WDLPS/DDLPS. Because the absence of CDK4 amplification is not specifically counterbalanced by a genomic alteration of the CCND1/CDK4/ P16INK4a/RB1/E2F pathway, CDK4 amplification may only represent a "MDM2-HMGA2-helper" in WDLPS/DDLPS tumorigenesis. (Clin Cancer Res 2009;15(18):5696-703)

show abstract

“…It has been reported that a target of CBX7 would be the CDKN2A/p16 tumor suppressor gene (11,12,33), suggesting that overexpression of CBX7 could enable cells to evade oncogeneinduced senescence; we then evaluated CDKN2A/p16 expression in (34,35), we show that CDKN2A/p16 is moderately overexpressed in PTCs and highly overexpressed in ATCs compared with normal thyroid tissues (Fig. 5).…”

Section: Cbx7 In Thyroid Carcinomasmentioning

confidence: 99%

Loss of the CBX7 Gene Expression Correlates with a Highly Malignant Phenotype in Thyroid Cancer

et al. 2008

View full text Add to dashboard Cite

Using gene expression profiling, we found that the CBX7 gene was drastically down-regulated in six thyroid carcinoma cell lines versus control cells. The aims of this study were to determine whether CBX7 is related to the thyroid cancer phenotype and to try to identify new tools for the diagnosis and prognosis of thyroid cancer. We thus evaluated CBX7 expression in various snap-frozen and paraffin-embedded thyroid carcinoma tissues of different degrees of malignancy by quantitative reverse transcription-PCR and immunohistochemistry, respectively. CBX7 expression progressively decreased with malignancy grade and neoplasia stage. Indeed, it decreased in an increasing percentage of cases going from benign adenomas to papillary (PTC), follicular, and anaplastic (ATC) thyroid carcinomas. This finding coincides with results obtained in rat and mouse models of thyroid carcinogenesis. CBX7 loss of heterozygosity occurred in 36.8% of PTC and in 68.7% of ATC. Restoration of CBX7 expression in thyroid cancer cells reduced growth rate, with a retention in the G 1 phase of the cell cycle, suggesting that CBX7 can contribute to the proliferation of the transformed thyroid cells. In conclusion, loss of CBX7 expression correlates with a highly malignant phenotype in thyroid cancer patients. [Cancer Res 2008;68(16):6770-8]

show abstract

The status of CDKN2A alpha (p16INK4A) and beta (p14ARF) transcripts in thyroid tumour progression

Cited by 39 publications

References 44 publications

Evidence of oncogene-induced senescence in thyroid carcinogenesis

Evidence of oncogene-induced senescence in thyroid carcinogenesis

Clinical and Biological Significance of CDK4 Amplification in Well-Differentiated and Dedifferentiated Liposarcomas

Loss of the CBX7 Gene Expression Correlates with a Highly Malignant Phenotype in Thyroid Cancer

Contact Info

Product

Resources

About