We sought to determine whether p15 is a useful immunohistochemical marker to distinguish Spitz nevi from spitzoid melanomas and to compare p15 and p16 staining in this population.
Methylation frequency of CLDN11 (OR, 25.56; 95% CI, 2.32-281.66; p = 0.008), MGMT (OR, 4.64; 95% CI, 1.98-10.90; p = 0.0004), p16 (OR, 4.31; 95% CI, 1.33-13.96; p = 0.01), and RASSF1A (OR, 10.10; 95% CI, 2.87-35.54; p = 0.0003) was significantly higher in metastasis melanoma compared with controls.
We found statistically significant differences between Spitz nevus and melanoma for the following features: pagetoid spread, atypia, maturation, elastosis, Kamino bodies, p16 expression, and the staining pattern of HMB45.
Melanocyte proliferation is activated by <i>BRAF</i><sup>V600E</sup>, then is arrested, but single nevi transform to melanomas. p16 controls arrest, and p16 loss may promote transformation.
We have performed a gain-of-function screen of 17,030 lentivirally expressed human open reading frames (ORFs) in a melanoma cell line containing an inducible p16 construct to identify such genes.
Although decreased p16 expression has been associated with melanoma formation, in recent work, p15 represented a primary effector of oncogene-induced senescence in nevomelanocytes that was diminished in melanomas.
Participants in all groups continued to rate photoprotection as highly effective in reducing melanoma risk and reported decreased beliefs that carrying the p16 mutation would inevitably lead to the development of melanoma.
Expression of p16 and mutated BRAF proteins was also evaluated in 17 conventional (nonspitzoid) melanomas with homozygous 9p21 loss and the 2 groups of ASTs.
We compared the gene expression profile of SFs from FM individuals with two distinct CDKN2A/p16 mutations (V126D-p16 and R87P-p16) with the gene expression profile of SFs from age-matched individuals without p16 mutations and with no family history of melanoma.
This study demonstrates the biological connection between the known melanoma genes p16 (CDKN2A) and BRAF in a normal physiological response to UVR in the skin, and highlights the importance of defects in this biological pathway to melanoma and squamous cell carcinoma development.
We conclude that HNSCC in young individuals should prompt clinicians to obtain a family history and consider that the patient may have a germline p16 defect that could predispose them to other cancers, including melanoma and pancreatic cancer.
The combination of MMR gene mutations and abnormalities of p16 or other molecular pathways is needed to induce melanocytic carcinogenesis in a familial setting as well as in sporadic MM.
Genetic and epigenetic analyses of the human 9p21 locus indicate that modifications of ARF occur independently of p16 inactivation in human melanoma and suggest that ARF is more frequently inactivated than p16.
Our data suggest that the P48T mutation of p16 is a strong melanoma-predisposing factor, but the fact that the heterozygous mutant parents have not yet exhibited melanoma or atypical moles indicates that the penetrance of this allele might depend on modifying factors.
To date several studies indicate the effective implication of p16 as a tumor suppressor gene with a major role in either the development or progression of human melanoma.
GenoMEL, comprising major familial melanoma research groups from North America, Europe, Asia, and Australia has created the largest familial melanoma sample yet available to characterize mutations in the high-risk melanoma susceptibility genes CDKN2A/alternate reading frames (ARF), which encodes p16 and p14ARF, and CDK4 and to evaluate their relationship with pancreatic cancer (PC), neural system tumors (NST), and uveal melanoma (UM).