p53 mutations are common in pancreatic cancer and are absent in chronic pancreatitis.
Pancreatic expression of the p53 tumor suppressor gene was studied in pancreatic adenocarcinomas and chronic pancreatitis. By immunohistochemistry, 16 of 34 (47%) cancers and none of the 24 chronic pancreatitis samples revealed nuclear staining. Sequence analysis indicated that 8 of 24 (33%) cancers were mutated for the p53 gene. Point substitutions occurred at codons 35, 105, 133, 213, 213, 258, and 299. A three base-pair in-frame insertion was identified between codons 261 and 262. None of 8 chronic pancreatitis samples exhibited p53 gene mutations. These data support a role for p53 gene alterations in human pancreatic cancer, and suggest that loss of its regulatory functions may constitute one of the differences between pancreatic cancer and chronic pancreatitis.
Department of Cancer Biology, Cleveland Clinic Foundation, OH 44195.
G
G
Casey
Y
Y
Yamanaka
H
H
Friess
M S
MS
Kobrin
M E
ME
Lopez
M
M
Buchler
H G
HG
Beger
M
M
Korc
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D002908:Chronic Disease; D003062:Codon / Q000235:genetics*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics*; D010195:Pancreatitis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics
D003062:Codon; D016159:Tumor Suppressor Protein p53