Loss of the Y chromosome is a frequent chromosomal imbalance in pancreatic cancer and allows differentiation to chronic pancreatitis.
In a study for the identification of genomic alterations in pancreatic cancer, representational difference analysis was used and led to the isolation of 2 distinct fragments, deleted on the Y chromosome in the xenografted tumor DNA of a male patient with an adenocarcinoma of the pancreas. Loss of Y chromosomal material was further studied in 11 pancreatic cancer cell lines of male origin, using PCR amplification of 5 sequence tagged sites (STSs) distributed along the Y chromosome; 8/11 cell lines exhibited a complete loss of the Y chromosome and 3 had deletions. To examine the status of the Y chromosome in situ, interphase FISH analysis was performed on paraffin sections from pancreatic carcinoma (n=7) and chronic pancreatitis (n=7) tissues, and the loss of Y-chromosomal STS-markers was studied in 6 xenograft tumors obtained from male pancreatic cancer patients. This analysis revealed that a loss of the Y chromosome occurs in vivo in primary pancreatic tumor cells, whereas the Y chromosome was intact in chronic pancreatitis. Our data suggest that loss of Y is a frequent event occurring in male pancreatic tumors. Although there is no evidence for a functional implication of Y chromosome loss, it effectively differentiates between a malignant and a benign condition as e.g. chronic pancreatitis. Thus, this genetic alteration may be of diagnostic use.
Wallrapp
C
C
Department of Internal Medicine I, University of Ulm, Ulm, Germany.
Hähnel
S
S
Boeck
W
W
Soder
A
A
Mincheva
A
A
Lichter
P
P
Leder
G
G
Gansauge
F
F
Sorio
C
C
Scarpa
A
A
Gress
T M
TM
D000818:Animals; D015139:Blotting, Southern; D002872:Chromosome Deletion; D002908:Chronic Disease; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D003937:Diagnosis, Differential; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics*; D010195:Pancreatitis / Q000175:diagnosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014998:Y Chromosome
D004273:DNA, Neoplasm; D005819:Genetic Markers