Impaired processing of DNA photoproducts and ultraviolet hypermutability with loss of p16INK4a or p19ARF

被引：36

作者：

Sarkar-Agrawal, P

Vergilis, I

Sharpless, NE

DePinho, RA

Rünger, TM

机构：

[1] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA

[2] Univ N Carolina, Lineberger Canc Res Ctr, Chapel Hill, NC 27599 USA

[3] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA

来源：

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2004年 / 96卷 / 23期

关键词：

D O I：

10.1093/jnci/djh307

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Reduced DNA repair has been linked to an increased risk of cutaneous malignant melanoma, but insights into the molecular mechanisms of that link are scarce. The INK4a/ARF (CDKN2a) locus, which codes for the p16(INK4a) and P19(ARF) proteins, is often mutated in sporadic and familial malignant melanoma, but it has not been directly associated with reduced DNA repair. We transfected unirradiated mouse fibroblast cells with UV-treated DNA to measure DNA repair in normal, p16(INK4a) mutant, P19(ARF) mutant, or double mutant mouse host cells. Loss of either p16(INK4a) or P19(ARF) reduced the ability of the cells to process UVinduced DNA damage, independent of cell cycle effects incurred by the loss. These results may further explain why INK4a/ARF mutations predispose to malignant melanoma, a UVinduced tumor.

引用

收藏

页码：1790 / 1793

页数：4

相关论文

共 31 条

[1] p53 and DNA damage-inducible expression of the xeroderma pigmentosum group C gene [J].

Adimoolam, S ;

Ford, JM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (20) :12985-12990

[2] XPD gene polymorphism and host characteristics in the association with cutaneous malignant melanoma risk [J].

Baccarelli, A ;

Calista, D ;

Minghetti, P ;

Marinelli, B ;

Albetti, B ;

Tseng, T ;

Hedayati, M ;

Grossman, L ;

Landi, G ;

Struewing, JP ;

Landi, MT .

BRITISH JOURNAL OF CANCER, 2004, 90 (02) :497-502

[3] Malignant melanoma: modern black plague and genetic black box [J].

Chin, L ;

Merlino, G ;

DePinho, RA .

GENES & DEVELOPMENT, 1998, 12 (22) :3467-3481

[4] Frequency of UV-inducible NRAS mutations in melanomas of patients with germline CDKN2A mutations [J].

Eskandarpour, M ;

Hashemi, J ;

Kanter, L ;

Ringborg, U ;

Platz, A ;

Hansson, J .

JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2003, 95 (11) :790-798

[5] Prevalence of germ-line mutations in p16, p19ARF, and CDK4 in familial melanoma: Analysis of a clinic-based population [J].

FitzGerald, MG ;

Harkin, DP ;

SilvaArrieta, S ;

MacDonald, DJ ;

Lucchina, LC ;

Unsal, H ;

ONeill, E ;

Koh, J ;

Finkelstein, DM ;

Isselbacher, KJ ;

Sober, AJ ;

Haber, DA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (16) :8541-8545

[6] The pathogenesis of melanoma induced by ultraviolet radiation [J].

Gilchrest, BA ;

Eller, MS ;

Geller, AC ;

Yaar, M .

NEW ENGLAND JOURNAL OF MEDICINE, 1999, 340 (17) :1341-1348

[7] Molecular genetics of familial cutaneous melanoma [J].

Haluska, FG ;

Hodi, FS .

JOURNAL OF CLINICAL ONCOLOGY, 1998, 16 (02) :670-682

[8] GERMLINE P16 MUTATIONS IN FAMILIAL MELANOMA [J].

HUSSUSSIAN, CJ ;

STRUEWING, JP ;

GOLDSTEIN, AM ;

HIGGINS, PAT ;

ALLY, DS ;

SHEAHAN, MD ;

CLARK, WH ;

TUCKER, MA ;

DRACOPOLI, NC .

NATURE GENETICS, 1994, 8 (01) :15-21

[9] Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2 [J].

Kamijo, T ;

Weber, JD ;

Zambetti, G ;

Zindy, F ;

Roussel, MF ;

Sherr, CJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (14) :8292-8297

[10] Components of the Rb pathway are critical targets of UV mutagenesis in a murine melanoma model [J].

Kannan, K ;

Sharpless, NE ;

Xu, J ;

O'Hagan, RC ;

Bosenberg, M ;

Chin, L .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (03) :1221-1225

← 1 2 3 4 →