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P53 MUTATIONS IN PANCREATIC-CARCINOMA AND EVIDENCE OF COMMON INVOLVEMENT OF HOMOCOPOLYMER TRACTS IN DNA MICRODELETIONS
Author(s): REDSTON MS, CALDAS C, SEYMOUR AB, HRUBAN RH, DACOSTA L, YEO CJ, KERN SE
Source: CANCER RESEARCH    Volume: 54    Issue: 11    Pages: 3025-3033    Published: JUN 1 1994  
Times Cited: 256     References: 52     
Abstract: Pancreatic adenocarcinoma is a major cause of cancer death, and yet little is known about its molecular pathogenesis. We identified p53 mutations in 19 (70%) of 27 primary pancreatic adenocarcinomas. Most were missense point mutations, and the mutations were distributed primarily within the evolutionarily conserved domains. Transitions predominated over transversions, and many of the transitions were at CpG dinucleotides. Intragenic deletions accounted for 32% of mutations and were associated with decreased survival (P = 0.0016). A review of 1937 published p53 mutations revealed that the occurrence of small (1-2 base pairs) microdeletions varied among different types of human neoplasms and that pancreatic adenocarcinoma had one of the highest frequencies (13% of 47 mutations, P = 0.0036). Many small deletions occurred in iterations of single bases, but this did not fully account for their pattern of distribution, and there was evidence for the involvement of homocopolymer (polypurine:polypyrimidine) tracts. This may represent a more widespread phenomenon, because microdeletions occur in similar sequence patterns in reports of somatic and germ line mutations among genes other than p53.
Document Type: Article
Language: English
Addresses:
1. JOHNS HOPKINS UNIV, SCH MED, DEPT PATHOL, BALTIMORE, MD 21205 USA
2. JOHNS HOPKINS UNIV, SCH MED, DEPT ONCOL, BALTIMORE, MD 21205 USA
3. JOHNS HOPKINS UNIV, SCH MED, DEPT SURG, BALTIMORE, MD 21205 USA
4. JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DIV TOXICOL SCI, BALTIMORE, MD 21205 USA
Publisher: AMER ASSOC CANCER RESEARCH, PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106
Subject Category: Oncology
IDS Number: NN724
ISSN: 0008-5472
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