Ml. Cher et al., COMPARATIVE GENOMIC HYBRIDIZATION, ALLELIC IMBALANCE, AND FLUORESCENCE IN-SITU HYBRIDIZATION ON CHROMOSOME-8 IN PROSTATE-CANCER, Genes, chromosomes & cancer, 11(3), 1994, pp. 153-162
Due to problems with primary tumor cell culture, conventional cytogene
tics has yielded little insightful information on chromosomal alterati
ons in prostate cancer. The primary aim of this study was to define th
e ability of comparative genomic hybridization (CGH) to detect and map
genetic deletions in prostate tumors. A secondary aim was to apply mu
ltiple assays to individual tumors as a means of deciphering the mecha
nisms of genetic alterations in prostate cancer. CGH results were comp
ared with allelic imbalance measurements at 29 distinct loci on chromo
some 8 in 18 specimens(17 malignant and I benign). CGH detected no cha
nges in cases where all informative PCR/RFLP loci were retained and de
tected all p arm deletions consisting of at least two loci. We estimat
e that in this study, the smallest deletions detected by CGH were appr
oximately 20-30 cM. Physical mapping of subchromosomal arm deletions b
y CGH correlated well with allelic imbalance mapping by PCR/RFLP: The
data agreed at 88% of loci on 8p and 92% of loci on 8q. Fluorescence i
n situ hybridization (FISH) with multiple centromere probes and DNA co
ntent flow cytometry (FCM) also was performed on selected specimens. F
ISH revealed two cases of chromosome 8 aneusomy. In these two cases an
d three others, CGH showed simultaneous p arm deletion and q arm gain,
suggesting isochromosome 8q formation. Together, these data suggested
that simple chromosomal aberrations were responsible for allelic loss
es on 8p and allelic gains on 8q in a significant number of prostate t
umors. We also used CGH to examine relative DNA sequence copy number t
hroughout the genome. Changes frequently associated with 8p loss inclu
de gains of 8q and losses of 13q, 16p, 16q, 17p, 17q, 20q, and Y. Case
s with 8p loss exhibited five times the number of alterations as did c
ases without 8p loss. (C) 1994 Wiley-Liss, Inc.