Detection of genetic alterations in pancreatic cancers by comparative genomic hybridization coupled with tissue microdissection and degenerate oligonucleotide primed polymerase chain reaction.
The aim of this study was to elucidate cytogenetic changes in pancreatic cancers (PCs) and to examine their clinical implications. We screened for genetic alterations in 32 primary PCs including 4 cases with distant organ metastasis using comparative genomic hybridization coupled with tissue microdissection and degenerate oligonucleotide primed polymerase chain reaction (DOP-PCR). The present study revealed frequent gains of chromosomes 13q and 15q and a loss of Xq in addition to a high prevalence of chromosomal imbalances. The average number of total genetic alterations and gains tended to be higher in N1 tumors (TNM classification) than in N0 tumors. The average number of amplifications was significantly higher in M1 tumors than in M0 tumors (p = 0.024). Gain/amplification of 20q was more frequently observed in M1 tumors than in M0 tumors (p = 0.016), and this change was also detected in all of 4 distant metastatic lesions. Losses of 6q, 8p, 9p, 17p, and 18q were recurrent in N0 and M0 tumors, and these alterations were also retained in N1 and M1 tumors. These observations suggest that these genetic losses contribute to the development of PCs and that increases in the DNA copy number confer an aggressive character on cancer cells. Especially, gain/amplification of 20q was associated with the potential of distant organ metastasis of tumor cells.
Harada
Tomohiko
T
Department of Pathology, Yamaguchi University School of Medicine, Japan. tharada@po.cc.yamaguchi-u.ac.jp
Okita
Kiwamu
K
Shiraishi
Kei
K
Kusano
Noriyoshi
N
Furuya
Tomoko
T
Oga
Atsunori
A
Kawauchi
Shigeto
S
Kondoh
Satoshi
S
Sasaki
Kohsuke
K
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D005629:Frozen Sections; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009693:Nucleic Acid Hybridization; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm