Pancreatology  2002;2(1):17-25 

Frequent deletions of tumor suppressor genes in pure pancreatic juice from
patients with tumoral or nontumoral pancreatic diseases.

Costentin L, Pages P, Bouisson M, Berthelemy P, Buscail L, Escourrou J,
Pradayrol L, Vaysse N.

INSERM, U531 Biologie, Pathologie Digestive et Departement de Gastroenterologie,
CHU Rangueil, 1, avenue J.-Poulhes F-31403 Toulouse, France.

BACKGROUND/AIMS: K-ras codon 12 mutation is the most frequent genetic alteration
in pancreatic cancer. Sensitivity and specificity of K-ras are not high enough
to detect all pancreatic cancers, especially at early stage. This study
investigated whether detection of p16 and/or DPC4 deletions along with K-ras
mutation in DNA samples could improve the definition of patients at risk of
pancreatic cancer. METHODS: K-ras mutations were investigated by sequencing. p16
and DPC4 homozygous deletions were studied using comparative multiplex
polymerase chain reaction of DNA in pancreatic juice sampled during endoscopic
retrograde pancreatography in 57 patients with either pancreatic cancer (group
I, 18 patients), chronic pancreatitis (group II, 20 patients), or nontumoral
pancreatobiliary disease (group III, 19 patients). RESULTS: The frequencies of
Ki-ras mutations were 61% in group I, 10% in group II, and 10.5% in group III.
The frequencies of p16 exon 2 and DPC4 deletions were, respectively, 28 and 36%
in group I, 50 and 58% in group II, and 24 and 36% in group III. CONCLUSIONS:
The combination of p16 and DPC4 deletions with K-ras mutation does not improve
the diagnosis of pancreatic cancer based on K-ras mutation alone. These data
suggest that tumor suppressor gene inactivation can occur with a high frequency
during nonmalignant pancreatic diseases.

PMID: 12120000 [PubMed - indexed for MEDLINE]