Hypermethylation of the CDKN2/p16 promoter during neoplastic progression in Barrett's esophagus

被引：148

作者：

Klump, B ^{[1
]}

Hsieh, CJ ^{[1
]}

Holzmann, K ^{[1
]}

Gregor, M ^{[1
]}

Porschen, R ^{[1
]}

机构：

[1] Univ Tubingen Hosp, Dept Med 1, D-72076 Tubingen, Germany

来源：

GASTROENTEROLOGY | 1998年 / 115卷 / 06期

关键词：

D O I：

10.1016/S0016-5085(98)70016-2

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background & Aims: Inactivation of the CDKN2/p16(INK4A) tumor-suppressor gene is one of the most frequent genetic alterations in human malignancies. In esophageal adenocarcinomas, mutations of the p16 gene or homozygous deletions of the gene locus 9p21 are rare. This study investigated whether p16 promoter hypermethylation is an alternative mechanism for p16 gene inactivation during neoplastic progression in Barrett's esophagus. Methods: A methylation-specific polymerase chain reaction protocol was applied. A total of 95 specimens from 14 patients with Barrett's esophagus were analyzed longitudinally. The p16 promoter status was compared with histomorphological findings. Results: p16 promoter hypermethylation was detected in 9 of the 10 patients who had displayed dysplasia at some time during surveillance, whereas none of the patients who had not displayed dysplasia during surveillance had p16 promoter hypermethylation. p16 promoter hypermethylation was detected in 3% (2 of 67) of the samples without dysplasia, 60% (3 of 5) of the samples with lesions indefinite for dysplasia, 55.6% (10 of 18) of the specimens with low-grade dysplasia, and 75% (3 of 4) of the specimens with high-grade dysplasia. Conclusions: These data suggest that p16 promoter hypermethylation is a common mechanism of p16 gene inactivation during neoplastic progression in Barrett's esophagus.

引用

页码：1381 / 1386

页数：6

共 40 条

[1]

Ahuja N, 1997, CANCER RES, V57, P3370

[2]

Barrett MT, 1996, ONCOGENE, V12, P1873

[3]

Barrett MT, 1996, ONCOGENE, V13, P1867

[4] CONTINUING CLIMB IN RATES OF ESOPHAGEAL ADENOCARCINOMA - AN UPDATE [J].

BLOT, WJ ;

DEVESA, SS ;

FRAUMENI, JF .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1993, 270 (11) :1320-1320

[5] RATES OF P16(MTS1) MUTATIONS IN PRIMARY TUMORS WITH 9P LOSS [J].

CAIRNS, P ;

MAO, L ;

MERLO, A ;

LEE, DJ ;

SCHWAB, D ;

EBY, Y ;

TOKINO, K ;

VANDERRIET, P ;

BLAUGRUND, JE ;

SIDRANSKY, D .

SCIENCE, 1994, 265 (5170) :415-416

[6] FREQUENCY OF HOMOZYGOUS DELETION AT P16/CDKN2 IN PRIMARY HUMAN TUMORS [J].

CAIRNS, P ;

POLASCIK, TJ ;

EBY, Y ;

TOKINO, K ;

CALIFANO, J ;

MERLO, A ;

MAO, L ;

HERATH, J ;

JENKINS, R ;

WESTRA, W ;

RUTTER, JL ;

BUCKLER, A ;

GABRIELSON, E ;

TOCKMAN, M ;

CHO, KR ;

HEDRICK, L ;

BOVA, GS ;

ISAACS, W ;

KOCH, W ;

SCHWAB, D ;

SIDRANSKY, D .

NATURE GENETICS, 1995, 11 (02) :210-212

[7] FREQUENT SOMATIC MUTATIONS AND HOMOZYGOUS DELETIONS OF THE P16 (MTS1) GENE IN PANCREATIC ADENOCARCINOMA [J].

CALDAS, C ;

HAHN, SA ;

DACOSTA, LT ;

REDSTON, MS ;

SCHUTTE, M ;

SEYMOUR, AB ;

WEINSTEIN, CL ;

HRUBAN, RH ;

YEO, CJ ;

KERN, SE .

NATURE GENETICS, 1994, 8 (01) :27-32

[8]

Costello JF, 1996, CANCER RES, V56, P2405

[9]

GONZALEZZULUETA M, 1995, CANCER RES, V55, P4531

[10] BARRETTS-ESOPHAGUS, DYSPLASIA, AND ADENOCARCINOMA [J].

HAGGITT, RC .

HUMAN PATHOLOGY, 1994, 25 (10) :982-993

← 1 2 3 4 →