Evaluation of genetic patterns in different tumor areas of intermediate-grade prostatic adenocarcinomas by high-resolution genomic array analysis.
Prostate cancer is known for its highly heterogeneous histological appearance. Data concerning the cytogenetic content of areas with different histology are sparse. We have genetically evaluated 10 prostatic adenocarcinomas with intermediate histopathological grades (Gleason score 7) that showed two distinctive growth patterns with different pathologies, that is, Gleason grades 3 and 4 (G3 and G4). The G3 and G4 tumor specimens were taken from spatially separated regions within the cancer mass. Array-based comparative genomic hybridization (aCGH) was performed to obtain genotypes from the 10 pairs of G3 and G4 cancer areas. The cancer DNAs were retrieved from formalin-fixed and paraffin-embedded tissues allowing optimal recognition and selection of target cells. A genome-wide 2,400-element BAC array that provided high-resolution detection of both deletions and amplifications was used. In the 20 G3 and G4 areas, 252 genomic aberrations (88 gains, 164 deletions) were noted, of which 86 were concurrent in G3 and G4 areas (34% overlap). Ninety-five of the 252 alterations were defined by a single BAC clone (54 gains, 41 deletions). Overlapping changes were more frequent for deletions (46%) than for gains (13%). Frequent coinciding deletions (> or = 20% of tumors) were seen on 8p (60%), 6q (30%), 1p (20%), 2q (20%), proximal 8q (20%), 10q (20%), 13q (20%), 16q (20%), and 18q (20%). A frequent overlapping gain (> or = 20% of tumors) was detected on distal 13q (20%). The patterns of imbalance could be found to coincide in the G3 and G4 areas of the majority of cancers. Array-based CGH can be used as a tool for the evaluation of genetic patterns in prostate cancer.
van Dekken
Herman
H
Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Paris
Pamela L
PL
Albertson
Donna G
DG
Alers
Janneke C
JC
Andaya
Armann
A
Kowbel
David
D
van der Kwast
Theodorus H
TH
Pinkel
Daniel
D
Schröder
Fritz H
FH
Vissers
Kees J
KJ
Wildhagen
Mark F
MF
Collins
Colin
C
D000230:Adenocarcinoma / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D000368:Aged; D020732:Cytogenetic Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011471:Prostatic Neoplasms / Q000145:classification* / Q000235:genetics* / Q000473:pathology
D004273:DNA, Neoplasm