Frequent clones of p53-mutated keratinocytes in normal human skin

被引:526
作者
Jonason, AS
Kunala, S
Price, GJ
Restifo, RJ
Spinelli, HM
Persing, JA
Leffell, DJ
Tarone, RE
Brash, DE
机构
[1] YALE UNIV, SCH MED, DEPT DERMATOL, NEW HAVEN, CT 06510 USA
[2] YALE UNIV, SCH MED, DEPT GENET, NEW HAVEN, CT 06510 USA
[3] YALE UNIV, SCH MED, DEPT SURG, SECT PLAST SURG, NEW HAVEN, CT 06510 USA
[4] YALE UNIV, SCH MED, YALE COMPREHENS CANC CTR, NEW HAVEN, CT 06510 USA
[5] CONNECTICUT CTR PLAST SURG, NEW HAVEN, CT 06511 USA
[6] NCI, BIOSTAT BRANCH, NIH, BETHESDA, MD 20205 USA
关键词
sunlight; ultraviolet; carcinogenesis; tumor promotion; clonal expansion;
D O I
10.1073/pnas.93.24.14025
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The multiple genetic hit model of cancer predicts that normal individuals should have stable populations of cancer-prone, but noncancerous, mutant cells awaiting further genetic hits. We report that whole-mount preparations of human skin contain clonal patches of p53-mutated keratinocytes, arising from the dermal-epidermal junction and from hair follicles, These clones, 60-3000 cells in size, are present at frequencies exceeding 10 cells per cm(2) and together involve as much as 4% of the epidermis. in sun-exposed skin, clones are both more frequent and larger than in sun-shielded skin, We conclude that, in addition to being a tumorigenic mutagen, sunlight acts as a tumor promoter by favoring the clonal expansion of p53-mutated cells, These combined actions of sunlight result in normal individuals carrying a substantial burden of keratinocytes predisposed to canter.
引用
收藏
页码:14025 / 14029
页数:5
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