Frequent loss of SMAD4/DPC4 protein in colorectal cancers

被引：112

作者：

Salovaara, R

Roth, S

Loukola, A

Launonen, V

Sistonen, P

Avizienyte, E

Kristo, P

Järvinen, H

Souchelnytskyi, S

Sarlomo-Rikala, M

Aaltonen, LA

机构：

[1] Univ Helsinki, Haartman Inst, Dept Med Genet, FIN-00014 Helsinki, Finland

[2] Finnish Red Cross & Blood Transfus Serv, FIN-00310 Helsinki, Finland

[3] Univ Helsinki, Cent Hosp, Dept Surg 2, FIN-00029 Helsinki, Finland

[4] Ludwig Inst Canc Res, S-75124 Uppsala, Sweden

[5] Ludwig Inst Canc Res, S-75124 Uppsala, Sweden

[6] Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland

[7] Univ Helsinki, Cent Hosp, Dept Oncol, FIN-00029 Helsinki, Finland

来源：

GUT | 2002年 / 51卷 / 01期

关键词：

D O I：

10.1136/gut.51.1.56

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background and aims: Loss of DNA sequences from chromosome 18q21 is a major genetic change in colorectal tumorigenesis. Multiple genes have been identified in this area. One of these, DPC4 (deleted in pancreatic cancer 4, also known as SMAD4), is mutated in a minor subset of colorectal carcinomas as well as in germlines of humans predisposed to colon tumours. Patients and methods: The involvement of SMAD4 in sporadic colorectal neoplasia was evaluated, by immunohistochemistry in 53 unselected cases and 27 cases displaying microsatellite instability. Results: SMAD4 expression was absent in 20 of 53 (38%) unselected colorectal carcinomas, and reduced in another 15 (28%) cases. However, 26 of 27 cancers displaying microsatellite instability and TGF-betaIIR mutations were positive for SMAD4 immunostaining. Conclusions: Loss of SMAD4 expression may play a more prominent role in colon cancer than anticipated based on genetic evidence, but not in mutator phenotype tumours.

引用

页码：56 / 59

页数：4

共 24 条

[1] CLUES TO THE PATHOGENESIS OF FAMILIAL COLORECTAL-CANCER [J].

AALTONEN, LA ;

PELTOMAKI, P ;

LEACH, FS ;

SISTONEN, P ;

PYLKKANEN, L ;

MECKLIN, JP ;

JARVINEN, H ;

POWELL, SM ;

JEN, J ;

HAMILTON, SR ;

PETERSEN, GM ;

KINZLER, KW ;

VOGELSTEIN, B ;

DELACHAPELLE, A .

SCIENCE, 1993, 260 (5109) :812-816

[2] Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease [J].

Aaltonen, LA ;

Salovaara, R ;

Kristo, P ;

Canzian, F ;

Hemminki, A ;

Peltomäki, P ;

Chadwick, RB ;

Kääriäinen, H ;

Eskelinen, M ;

Järvinen, H ;

Mecklin, JP ;

de la Chapelle, A ;

Percesepe, A ;

Ahtola, H ;

Härkönen, N ;

Julkunen, R ;

Kangas, E ;

Ojala, S ;

Tulikoura, J ;

ValKamo, E .

NEW ENGLAND JOURNAL OF MEDICINE, 1998, 338 (21) :1481-1487

[3] IDENTIFICATION OF A CHROMOSOME-18Q GENE THAT IS ALTERED IN COLORECTAL CANCERS [J].

FEARON, ER ;

CHO, KR ;

NIGRO, JM ;

KERN, SE ;

SIMONS, JW ;

RUPPERT, JM ;

HAMILTON, SR ;

PREISINGER, AC ;

THOMAS, G ;

KINZLER, KW ;

VOGELSTEIN, B .

SCIENCE, 1990, 247 (4938) :49-56

[4] DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1 [J].

Hahn, SA ;

Schutte, M ;

Hoque, ATMS ;

Moskaluk, CA ;

daCosta, LT ;

Rozenblum, E ;

Weinstein, CL ;

Fischer, A ;

Yeo, CJ ;

Hruban, RH ;

Kern, SE .

SCIENCE, 1996, 271 (5247) :350-353

[5] Identification of c-MYC as a target of the APC pathway [J].

He, TC ;

Sparks, AB ;

Rago, C ;

Hermeking, H ;

Zawel, L ;

da Costa, LT ;

Morin, PJ ;

Vogelstein, B ;

Kinzler, KW .

SCIENCE, 1998, 281 (5382) :1509-1512

[6] TGF-beta signalling from cell membrane to nucleus through SMAD proteins [J].

Heldin, CH ;

Miyazono, K ;

tenDijke, P .

NATURE, 1997, 390 (6659) :465-471

[7] Mutations in the SMAD4/DPC4 gene in juvenile polyposis [J].

Howe, JR ;

Roth, S ;

Ringold, JC ;

Summers, RW ;

Järvinen, HJ ;

Sistonen, P ;

Tomlinson, IPM ;

Houlston, RS ;

Bevan, S ;

Mitros, FA ;

Stone, EM ;

Aaltonen, LA .

SCIENCE, 1998, 280 (5366) :1086-1088

[8] Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis [J].

Howe, JR ;

Bair, JL ;

Sayed, MG ;

Anderson, ME ;

Mitros, FA ;

Petersen, GM ;

Velculescu, VE ;

Traverso, G ;

Vogelstein, B .

NATURE GENETICS, 2001, 28 (02) :184-187

[9] Lessons from hereditary colorectal cancer [J].

Kinzler, KW ;

Vogelstein, B .

CELL, 1996, 87 (02) :159-170

[10]

Korchynskyi O, 1999, INT J CANCER, V82, P197, DOI 10.1002/(SICI)1097-0215(19990719)82:2<197::AID-IJC8>3.0.CO

← 1 2 3 →