Frequent deletions of tumor suppressor genes in pure pancreatic juice from patients with tumoral or nontumoral pancreatic diseases

被引:32
作者
Costentin, L
Pagès, P
Bouisson, M
Berthelémy, P
Buscail, L
Escourrou, J
Pradayrol, L
Vaysse, N
机构
[1] CHU Rangueil, INSERM U 531, IFR 31, F-31403 Toulouse, France
[2] CHU Rangueil, Dept Gastroenterol, F-31403 Toulouse, France
关键词
p16; DPC4; pancreatic juice; pancreatic cancer; chronic pancreatitis;
D O I
10.1159/000049443
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/Aims: K-ras codon 12 mutation is the most frequent genetic alteration in pancreatic cancer. Sensitivity and specificity of K-ras are not high enough to detect all pancreatic cancers, especially at early stage. This study investigated whether detection of p16 and/or DPC4 deletions along with K-ras mutation in DNA samples could improve the definition of patients at risk of pancreatic cancer. Methods: K-ras mutations were investigated by sequencing. p16 and DPC4 homozygous deletions were studied using comparative multiplex polymerase chain reaction of DNA in pancreatic juice sampled during endoscopic retrograde pancreatography in 57 patients with either pancreatic cancer (group I, 18 patients), chronic pancreatitis (group II, 20 patients); or nontumoral pancreatobiliary disease (group III, 19 patients). Results: The frequencies of Ki-ras mutations were 61% in group I, 10% in group II, and 10.5% in group Ill. The frequencies of p 16 exon 2 and DPC4 deletions were, respectively, 28 and 36% in group I, 50 and 58% in group II, and 24 and 36% in group III. Conclusions: The combination of p16 and DPC4 deletions with K-ras mutation does not improve the diagnosis of pancreatic cancer based on K-ras mutation alone. These data suggest that tumor suppressor gene inactivation can occur with a high frequency during nonmalignant pancreatic diseases. Copyright (C) 2002 S. Karger AG, Basel and IAP.
引用
收藏
页码:17 / 25
页数:9
相关论文
共 38 条
[1]   MOST HUMAN CARCINOMAS OF THE EXOCRINE PANCREAS CONTAIN MUTANT C-K-RAS GENES [J].
ALMOGUERA, C ;
SHIBATA, D ;
FORRESTER, K ;
MARTIN, J ;
ARNHEIM, N ;
PERUCHO, M .
CELL, 1988, 53 (04) :549-554
[2]   PANCREATOGRAPHY IN CHRONIC-PANCREATITIS - INTERNATIONAL DEFINITIONS [J].
AXON, ATR ;
CLASSEN, M ;
COTTON, PB ;
CREMER, M ;
FREENY, PC ;
LEES, WR .
GUT, 1984, 25 (10) :1107-1112
[3]   FREQUENT MUTATIONS OF CDKN2 IN PRIMARY PANCREATIC ADENOCARCINOMAS [J].
BARTSCH, D ;
SHEVLIN, DW ;
TUNG, WS ;
KISKER, O ;
WELLS, SA ;
GOODFELLOW, PJ .
GENES CHROMOSOMES & CANCER, 1995, 14 (03) :189-195
[4]   IDENTIFICATION OF K-RAS MUTATIONS IN PANCREATIC-JUICE IN THE EARLY DIAGNOSIS OF PANCREATIC-CANCER [J].
BERTHELEMY, P ;
BOUISSON, M ;
ESCOURROU, J ;
VAYSSE, N ;
RUMEAU, JL ;
PRADAYROL, L .
ANNALS OF INTERNAL MEDICINE, 1995, 123 (03) :188-191
[5]  
BRENTNALL TA, 1995, CANCER RES, V55, P4264
[6]   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
[7]  
CALDAS C, 1994, CANCER RES, V54, P3568
[8]  
CUBILLA AL, 1976, CANCER RES, V36, P2690
[9]  
Gansauge S, 1998, BRIT J SURG, V85, P337
[10]   HIGH-FREQUENCY OF KI-RAS CODON-12 MUTATIONS IN PANCREATIC ADENOCARCINOMAS [J].
GRUNEWALD, K ;
LYONS, J ;
FROHLICH, A ;
FEICHTINGER, H ;
WEGER, RA ;
SCHWAB, G ;
JANSSEN, JWG ;
BARTRAM, CR .
INTERNATIONAL JOURNAL OF CANCER, 1989, 43 (06) :1037-1041