Ja. Macoska et al., FLUORESCENCE IN-SITU HYBRIDIZATION ANALYSIS OF 8P ALLELIC LOSS AND CHROMOSOME-8 INSTABILITY IN HUMAN PROSTATE-CANCER, Cancer research, 54(14), 1994, pp. 3824-3830
Cytogenetic and molecular biological studies have demonstrated deletio
n of sequences that map to the short arm of chromosome 8 (8p) in tumor
s from several organ systems, including sequences that map within or n
ear 8p22 in human prostate tumors. Recent studies in our laboratory ha
ve suggested that deletion of sequences on 8p may be concurrent with a
lterations in dosage for chromosome 8. In order to further investigate
this finding, the present study has applied fluorescence in situ hybr
idization (FISH) techniques to determine the status of chromosome 8 in
prostate tumors that have undergone deletion of sequences at 8p22. Do
sage of 8p22 sequences was assayed utilizing unique sequence cosmid DN
A probes by FISH and confirmed by amplification of microsatellite sequ
ences by polymerase chain reaction (PCR). Chromosome 8 dosage was assa
yed by FISH utilizing both unique sequence cosmid probe DNA (specific
to the 8q13.1-q13.3 chromosomal region) and pericentromeric probe DNA.
FISH analysis of 10 specimens of normal or benign prostatic hyperplas
ia tissues paired with 9 tumor and one prostatic intraepithelial neopl
asia tissues from the same patients for dosage at 8p, 8cen, and 8q, an
d PCR analysis for dosage at 8p, demonstrated that (a) FISH provided a
more precise means of evaluating allelic loss than PCR in prostate ti
ssue; (b) 8p22 sequence losses occurred frequently in prostate tumors;
(c) 8p22 sequence losses were most often detected in the absence of 8
cen or 8q sequence dosage alterations, although they were sometimes ac
companied by gain or loss of 8cen or 8q sequences; and (d) the pattern
of 8p22 sequence losses was most often widespread rather than focal.
This study is the first to describe FISH analysis of interphase nuclei
within tissue sections using cosmid probe DNAs.