Low frequency of p16INK4a alterations in insulinomas

被引：47
作者：
Bartsch, DK
Kersting, M
Wild, A
Ramaswamy, A
Gerdes, B
Schuermann, M
Simon, B
Rothmund, M
机构：
[1] Univ Marburg, Dept Surg, D-35043 Marburg, Germany
[2] Univ Marburg, Dept Oncol, D-35043 Marburg, Germany
[3] Univ Marburg, Dept Pathol, D-35043 Marburg, Germany
[4] Univ Marburg, Dept Gastroenterol & Endocrinol, D-35043 Marburg, Germany
来源：
DIGESTION | 2000年 / 62卷 / 2-3期
关键词：
insulinoma; p(16INK4a) tumor-suppressor gene;
D O I：
10.1159/000007810
中图分类号：
R57 [消化系及腹部疾病];
学科分类号：
摘要：
Background/Aims: The molecular mechanisms contributing to the tumorigenesis of insulinomas are poorly understood. Disruption of the cell cycle due to inactivation of the p16(INK4a) tumor-suppressor gene was identified in a variety of human tumors, including gastrinomas and nonfunctioning endocrine pancreatic carcinomas. In this study the role of p16(INK4a) i, the tumorigenesis of insulinomas was evaluated. Merhods: Seventeen insulinomas (14 benign, 3 malignant) were analyzed for genetic alterations in the p16(INK4a) tumor-suppressor gene by SSCP, PCR-based deletion and methylation-specific assays, p16 expression was determined by immunohistochemistry. Results: One malignant insulinoma showed a homozygous deletion of p16(INK4a) and another two benign insulinomas revealed aberrant methylation of the p16(INK4a) promoter region. All three tumors lacked p16 expression according to immunohistochemistry. None of the insulinomas carried intragenic p16(INK4a) mutations. In total, 17% of insulinomas had p16(INK4a) alterations. Conclusions: The p16(INK4a) tumor-suppressor gene contributes to tumorigenesis in only a small subset of insulinomas. Copyright (C) 2000 S. Karger AG. Basel.
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页码：171 / 177
页数：7
相关论文
共 24 条
[1]   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
[2]   Mutations of the DPC4/Smad4 gene in neuroendocrine pancreatic tumors [J].
Bartsch, D ;
Hahn, SA ;
Danichevski, KD ;
Ramaswamy, A ;
Bastian, D ;
Galehdari, H ;
Barth, P ;
Schmiegel, W ;
Simon, B ;
Rothmund, M .
ONCOGENE, 1999, 18 (14) :2367-2371
[3]  
BARTSCH D, 1999, LANGENBECKS ARCH CHI, P13
[4]   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
[5]   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
[6]   Analysis of the retinoblastoma tumour suppressor gene in pancreatic endocrine tumours [J].
Chung, DC ;
Smith, AP ;
Louis, DN ;
GraemeCook, F ;
Warshaw, AL ;
Arnold, A .
CLINICAL ENDOCRINOLOGY, 1997, 47 (05) :523-528
[7]  
EDIS AJ, 1984, MANUAL ENDODRINE SUR
[8]  
GONZALEZZULUETA M, 1995, CANCER RES, V55, P4531
[9]   PLASMA PROINSULIN-LIKE COMPONENT IN INSULINOMA - A 25-YEAR EXPERIENCE [J].
GORDEN, P ;
SKARULIS, MC ;
ROACH, P ;
COMI, RJ ;
FRAKER, DL ;
NORTON, JA ;
ALEXANDER, HR ;
DOPPMAN, JL .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1995, 80 (10) :2884-2887
[10]   Methylation-specific PCR: A novel PCR assay for methylation status of CpG islands [J].
Herman, JG ;
Graff, JR ;
Myohanen, S ;
Nelkin, BD ;
Baylin, SB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (18) :9821-9826
123