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.
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.
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.
This partial functional defect may complement the clearly defective p16 del (62-69) mutant and thus contribute to melanoma development in patients carrying the 24bp deletion in CDKN2A.
MeWo cells, which alone expressed intrinsic wild-type p16 among six melanoma cell lines examined, showed higher radiosensitivity in comparison with the other five melanoma cells.
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.
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.
At present, the most useful methods of risk assessment are those performed on the following genes: BRCA1 and BRCA2 especially for hereditary breast and ovarian cancer, hMLH1 and hMSH2 for hereditary non polyposis colorectal cancer, APC for familial adenomatous polyposis, ret for medullary thyroid carcinoma, p53 for the Li-Fraumeni syndrome, p16 for melanoma and RB1 for retinoblastoma.
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.
A cytostatic effect of flavopiridol on the growth of six melanoma cell lines with a mutated or non-expressed p16 (p16-) was seen at low concentrations of flavopiridol (mean 50% inhibitory concentration [IC(50)] = 12.5 nM), while the three melanoma cell lines with intact p16 (p16+) required higher concentrations (mean IC(50) = 25 nM) to produce this effect.
Taken together with a predominance of UV-induced mutations in the CDKN2/ p16 gene demonstrated in melanoma cell lines, our data support a role of sunlight exposure in the etiology of malignant 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.
In an example presented regarding a planned study of the p16 gene and its role in melanoma, a conventional case-control study may require up to 70 times as many subjects to achieve equivalent precision to the study of second primaries.