Loss of Expression of the p16 Gene Is Frequent in Malignant Skin Tumors

Chang, Ting Gung; Wang, Jyh Seng; Chen, Lee Wei; Hsu, Ching Yi; Chang, Hung‐Wen; Chen, Jin Shyr; Cho, Chung Lung

doi:10.1006/bbrc.1996.5891

Cited by 25 publications

(18 citation statements)

References 12 publications

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“…The lower frequency of p16 abnormalities in BCCs could probably be explained by the fact that in this tumor, tumorigenesis preferentially occurs through abnormalities of Shh or p53 signalling pathways. Yet, loss of expression of p16INKA protein was previously reported in BCC (Chang et al, 1997), and therefore, inactivation of p16 may be relevant in oncogenesis of some BCCs.…”

Section: Tyr129stopmentioning

confidence: 92%

P16 UV mutations in human skin epithelial tumors

Soufir¹,

Molès²,

Vilmer³

et al. 1999

Oncogene

103

100

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The p16 gene expresses two alternative transcripts (p16a and p16b) involved in tumor suppression via the retinoblastoma (Rb) or p53 pathways. Disruption of these pathways can occur through inactivation of p16 or p53, or activating mutations of cyclin dependant kinase 4 gene (Cdk4). We searched for p16, Cdk4 and p53 gene mutations in 20 squamous cell carcinomas (SSCs), 1 actinic keratosis (AK), and 28 basal cell carcinomas (BCCs), using PCR-SSCP. A deletion and methylation analysis of p16 was also performed. Six dierent mutations (12%) were detected in exon 2 of p16 (common to p16a and p16b), in ®ve out of 21 squamous lesions (24%) (one AK and four SCCs) and one out of 28 BCCs (3.5%). These included four (66%) ultraviolet (UV)-type mutations (two tandems CC : GG to TT : AA transitions and two C : G to T : A transitions at dipyrimidic site) and two transversions. P53 mutations were present in 18 samples (37%), mostly of UV type. Of these, only two (one BCC and one AK) harboured simultaneously mutations of p16, but with no consequence on p16b transcript. Our data demonstrate for the ®rst time the presence of p16 UV induced mutations in non melanoma skin cancer, particularly in the most aggressive SCC type, and support that p16 and p53 are involved in two independent pathways in skin carcinogenesis.

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Section: Tyr129stopmentioning

confidence: 92%

P16 UV mutations in human skin epithelial tumors

Soufir¹,

Molès²,

Vilmer³

et al. 1999

Oncogene

103

100

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“…LOH encompassing 9p21-p22 has led to the hypothesis that the tumor-suppressor gene CDKN2A may play a critical role in cutaneous SCC development. Mutational analysis and loss of transcript expression further suggest that inactivation of CDKN2A is important for SCC progression (Chang et al, 1997;Kubo et al, 1997;Soufir et al, 1999;Mortier et al, 2002). Loss at 3p in SCC gave rise to the potential involvement of the known tumor-suppressor gene FHIT (3p14.2), whose involvement in oral SCC is established (Tanimoto et al, 2000).…”

Section: Loss Of Heterozygosity Studies In Nmscmentioning

confidence: 99%

Cytogenetic alterations in nonmelanoma skin cancer: A review

Ashton

Carless

Griffiths

2005

Genes Chromosomes & Cancer

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Since the advent of cytogenetic analysis, knowledge about fundamental aspects of cancer biology has increased, allowing the processes of cancer development and progression to be more fully understood and appreciated. Classical cytogenetic analysis of solid tumors had been considered difficult, but new advances in culturing techniques and the addition of new cytogenetic technologies have enabled a more comprehensive analysis of chromosomal aberrations associated with solid tumors. Our purpose in this review is to discuss the cytogenetic findings on a number of nonmelanoma skin cancers, including squamous- and basal cell carcinomas, keratoacanthoma, squamous cell carcinoma in situ (Bowen's disease), and solar keratosis. Through classical cytogenetic techniques, as well as fluorescence-based techniques such as fluorescence in situ hybridization and comparative genomic hybridization, numerous chromosomal alterations have been identified. These aberrations may aid in further defining the stages and classifications of nonmelanoma skin cancer and also may implicate chromosomal regions involved in progression and metastatic potential. This information, along with the development of newer technologies (including laser capture microdissection and comparative genomic hybridization arrays) that allow for more refined analysis, will continue to increase our knowledge about the role of chromosomal events at all stages of cancer development and progression and, more specifically, about how they are associated with nonmelanoma skin cancer.

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“…1 In squamous cell carcinomas, p16 expression is complex and may be due to CDKN2A (INK4a) mutations, 7,8,10 which lead to overexpression of p16, 9,10 inactivating point mutations, and most commonly, epigenetic silencing of the CDKN2A promoter gene, resulting in loss of heterozygosity 5-7,10 leading to decreased expression of p16. [5][6][7]10 PCR molecular studies now link many actinic keratosestraditionally thought to be only induced by UV irradiation-to 19 demonstrated viral loads of EV-related HPV detected in both actinic keratoses and squamous cell carcinomas using sophisticated quantitative PCR methods of detection; however, the authors were cautious enough not to exclude a carrier state as another explanation for HPV detection within these lesions. Other studies have associated high-risk HPV genotypes to extragenital Bowen's disease with p16 overexpression.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] These include mutations (both inactivating and structural), loss of heterozygosity, or epigenetic silencing via methylation of the promoter region of the CDKN2A (INK4a) gene in cutaneous neoplasms. Therefore, unlike in cervix or tonsils, in skin the overexpression of p16 is more complex and related to a disruption of the cell cycle at the G1-S checkpoint and may not be related to HPV.…”

Section: Introductionmentioning

confidence: 99%

p16 Expression in Conventional and Desmoplastic Trichilemmomas

Hilliard

Wakefield²,

Krahl³

et al. 2009

The American Journal of Dermatopathology

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The expression of p16 in cutaneous neoplasms is upregulated in melanocytic neoplasms, ultraviolet radiation-induced neoplasms, such as actinic keratoses and squamous cell carcinomas, and in lesions related to human papillomavirus, such as Bowen's disease and bowenoid papulosis. In cervical dysplasia and tonsillar carcinoma, there is such a close relationship between p16 and human papillomavirus (HPV) to the extent that p16 immunostaining is used as a surrogate marker for the presence of HPV proteins. In this study we were interested in the expression pattern of p16 in trichilemmomas. Twenty-six conventional and 19 desmoplastic trichilemmomas were immunohistochemically stained for p16. p16 immunostaining was noted in the majority of conventional (80.8%) and desmoplastic trichilemmomas (73.7%). The staining pattern was both nuclear and cytoplasmic. The staining intensity was more pronounced in the desmoplastic variant. We describe for the first time p16 expression in trichilemmomas and discuss our findings in conjunction with p16 expression found in other cutaneous neoplasms. Additionally, the relationship of p16 to HPV infection is critically evaluated.

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Loss of Expression of the p16 Gene Is Frequent in Malignant Skin Tumors

Cited by 25 publications

References 12 publications

P16 UV mutations in human skin epithelial tumors

P16 UV mutations in human skin epithelial tumors

Cytogenetic alterations in nonmelanoma skin cancer: A review

p16 Expression in Conventional and Desmoplastic Trichilemmomas

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