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| K-RAS AND P53 GENE-MUTATIONS IN PANCREATIC-CANCER - DUCTAL AND NONDUCTAL TUMORS PROGRESS THROUGH DIFFERENT GENETIC LESIONS |
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| Author(s): PELLEGATA NS, SESSA F, RENAULT B, BONATO M, LEONE BE, SOLCIA E, RANZANI GN |
| Source: CANCER RESEARCH Volume: 54 Issue: 6 Pages: 1556-1560 Published: MAR 15 1994 |
| Times Cited: 263 References: 38 |
| Abstract: We studied K-ras and p53 gene mutations in a panel of 57 primary pancreatic cancers including ductal and nonductal tumors. DNAs were obtained from formalin fixed, paraffin-embedded material. Target sequences were amplified by polymerase chain reaction and analyzed by denaturing gradient gel electrophoresis and sequencing. Both K-ras and p53 genes were frequently mutated in ductal cancers (25 of 35, 71.4%; 18 of 35, 51.4%, respectively). K-ras mutations were confined to the second position of codon 12 where base transitions and transversions were equally observed. p53 changes were mainly missense mutations. Transitions and transversions were found equally with a prevalence of G:C --> A:T changes among transitions. No gene alterations were present in the 6 exocrine nonductal tumors and (with one exception) in the 12 endocrine tumors analyzed. Our results indicate that mutated K-ras and p53 genes can cooperate in the establishment of ductal pancreatic cancers, whereas other genetic events have to be present in nonductal tumors. Moreover, K-ras alterations may represent an early event in ductal tumorigenesis, as suggested both by the high gene mutation frequency and by the presence of mutations in low-grade tumors. On the contrary, p53 gene changes seem to represent an event required for the malignancy progression of ductal tumors from lower to higher grades. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV PAVIA, DEPT GENET & MICROBIOL, I-27100 PAVIA, ITALY
2. OSPED CIRCOLO VARESE, DEPT PATHOL, I-21100 VARESE, ITALY
3. OSPED SAN RAFFAELE, IST RICOVERO & CURA CARATTERE SCI, DEPT PATHOL, MILAN, ITALY
4. UNIV PAVIA, DEPT HUMAN PATHOL, I-27100 PAVIA, ITALY
5. OSPED S MATTEO, IST RICOVERO & CURA CARATTERE SCI, I-27100 PAVIA, ITALY |
| Publisher: AMER ASSOC CANCER RESEARCH, PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 |
| Subject Category: Oncology |
| IDS Number: NA887 |
| ISSN: 0008-5472 |
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