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Mitochondrial DNA D-loop in pancreatic cancer: somatic mutations are epiphenomena while the germline 16519 T variant worsens metabolism and outcome.
- Source :
-
American journal of clinical pathology [Am J Clin Pathol] 2006 Oct; Vol. 126 (4), pp. 593-601. - Publication Year :
- 2006
-
Abstract
- We ascertained the frequency of mitochondrial DNA (mtDNA) D-loop region somatic mutations in pancreatic cancer (PC) and verified whether polymorphisms were linked to diagnosis, prognosis, and PC-associated diabetes mellitus (DM) in 99 PC cases, 42 chronic pancreatitis (CP) cases, 18 pancreatobiliary tract tumors, and 87 healthy control subjects (CSs). Tissue samples were obtained from 19 patients with PC and 5 with CP. The D-loop region was sequenced from all tissue samples and from blood DNA of the same patients and 12 CSs. D-loop somatic mutations were found in 3 PC tissue samples (16%). Four single nucleotide polymorphisms (SNPs; T152C, T16189C, T16519C, A73G), more frequently found in PC than in CS, were analyzed by denaturing high-performance liquid chromatography-restriction fragment length polymorphism using blood DNA as the starting template in all cases. The T allele of 16519 SNP correlated with DM. The survival of patients with PC correlated with tumor stage and grade and with DM at diagnosis. When survival analysis was performed considering only patients with locally advanced disease, the T allele of mtDNA 16519 SNP correlated with shorter life expectancy. mtDNA D-loop somatic mutations, rarely found in PC, cannot be considered causative events for this tumor type and probably are epiphenomena; the mtDNA D-loop 16519 variant, which worsens PC prognosis, seems to be a predisposing genetic factor for DM.
- Subjects :
- Adenocarcinoma complications
Adenocarcinoma metabolism
Adenocarcinoma mortality
Adult
Aged
Aged, 80 and over
Bile Duct Neoplasms complications
Bile Duct Neoplasms genetics
Bile Duct Neoplasms metabolism
DNA Mutational Analysis
Diabetes Mellitus etiology
Diabetes Mellitus genetics
Diabetes Mellitus metabolism
Female
Genetic Predisposition to Disease
Humans
Male
Middle Aged
Neoplasm Staging
Pancreatic Neoplasms complications
Pancreatic Neoplasms metabolism
Pancreatic Neoplasms mortality
Pancreatitis, Chronic complications
Pancreatitis, Chronic genetics
Pancreatitis, Chronic metabolism
Survival Rate
Adenocarcinoma genetics
DNA, Mitochondrial genetics
Germ-Line Mutation
Pancreatic Neoplasms genetics
Point Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9173
- Volume :
- 126
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of clinical pathology
- Publication Type :
- Academic Journal
- Accession number :
- 16938655
- Full Text :
- https://doi.org/10.1309/GQFCCJMH5KHNVX73