Analysis of germline gene copy number variants of patients with sporadic pancreatic adenocarcinoma reveals specific variations.
OBJECTIVE
The rapid fatality of pancreatic cancer is, in large part, the result of diagnosis at an advanced stage in the majority of patients. Identification of individuals at risk of developing pancreatic adenocarcinoma would be useful to improve the prognosis of this disease. There is presently no biological or genetic indicator allowing the detection of patients at risk. Our main goal was to identify copy number variants (CNVs) common to all patients with sporadic pancreatic cancer.


METHODS
We analyzed gene CNVs in leukocyte DNA from 31 patients with sporadic pancreatic adenocarcinoma and from 93 matched controls. Genotyping was performed with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix).


RESULTS
We identified 431 single nucleotide polymorphism (SNP) probes with abnormal hybridization signal present in the DNA of all 31 patients. Of these SNP probes, 284 corresponded to 3 or more copies and 147 corresponded to 1 or 0 copies. Several cancer-associated genes were amplified in all patients. Conversely, several genes supposed to oppose cancer development were present as single copy.


CONCLUSIONS
These data suggest that a set of 431 CNVs could be associated with the disease. This set could be useful for early diagnosis.
Section of Medical Oncology, Department of Surgical, Oncological and Stomatological Sciences,University of Palermo, Palermo, Italy.
Daniele
D
Fanale
Juan Lucio
JL
Iovanna
Ezequiel Luis
EL
Calvo
Patrice
P
Berthezene
Pascal
P
Belleau
Jean Charles
JC
Dagorn
Chiara
C
Ancona
Giovanna
G
Catania
Paolo
P
D'Alia
Antonio
A
Galvano
Eliana
E
Gulotta
Silvia
S
Lo Dico
Francesco
F
Passiglia
Giuseppe
G
Bronte
Massimo
M
Midiri
Giuseppe
G
Lo Re
Giuseppe
G
Cicero
Viviana
V
Bazan
Antonio
A
Russo
D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis
D004273:DNA, Neoplasm