PMID- 9665474
OWN - NLM
STAT- MEDLINE
DCOM- 19980723
LR  - 20240317
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 153
IP  - 1
DP  - 1998 Jul
TI  - Genetic alterations in hormone-refractory recurrent prostate carcinomas.
PG  - 141-8
AB  - To study the genetic basis of tumor progression, we have screened 37 
      hormone-refractory prostate carcinomas for genetic changes by comparative genomic 
      hybridization (CGH). All recurrent tumors showed genetic aberrations, with a mean 
      total number of changes per tumor of 11.4 (range, 3 to 23). The most common 
      genetic aberrations were losses of 8p (72.5%), 13q (50%), 1p (50%), 22 (45%), 19 
      (45%), 10q (42.5%), and 16q (42.5%) and gains of 8q (72.5%), 7q (40%), Xq 
      (32.5%), and 18q (32.5%). The CGH results were further validated with 
      fluorescence in situ hybridization (FISH) using probes for pericentromeric 
      regions of chromosomes 7, 8, and 18 as well as probes for caveolin (7q31), c-myc 
      (8q24), and bcl-2 (18q21.3). In addition, the samples had previously been 
      analyzed for androgen receptor gene copy number. CGH and FISH results were 
      concordant in 78% of cases. Seventeen of twenty-two tumors showed an increased 
      copy number of c-myc by FISH. However, only 5 of 17 (29%) of the cases showed 
      high-level (more than threefold) amplification. Both CGH and FISH findings 
      suggested that in most of the cases 8q gain involves the whole q-arm of the 
      chromosome. Four of seventeen (24%) cases showed increased copy number of bcl-2 
      by FISH; however, no high-level amplifications were found. To evaluate the clonal 
      relationship of the primary and recurrent tumors, six primary-recurrent tumor 
      pairs from the same patients were studied by CGH. In three of six cases (50%), 
      the recurrent tumor had more than one-half of the aberrations found in the 
      corresponding primary tumor, indicating a close clonal relationship. In the rest 
      of the cases, such a linear clonal relationship was less evident. Altogether, 
      these results suggest that recurrent prostate carcinomas are genetically 
      unstable. The resulting heterogeneity may well underlie the poor responsiveness 
      of hormone-refractory tumors to treatment.
FAU - Nupponen, N N
AU  - Nupponen NN
AD  - Laboratory of Cancer Genetics, Institute of Medical Technology, University of 
      Tampere and Tampere University Hospital, Finland.
FAU - Kakkola, L
AU  - Kakkola L
FAU - Koivisto, P
AU  - Koivisto P
FAU - Visakorpi, T
AU  - Visakorpi T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (CAV1 protein, human)
RN  - 0 (Caveolin 1)
RN  - 0 (Caveolins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (Receptors, Androgen)
SB  - IM
MH  - Carcinoma/*genetics
MH  - Caveolin 1
MH  - *Caveolins
MH  - *Chromosome Aberrations
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Membrane Proteins/genetics
MH  - Neoplasm Recurrence, Local/genetics
MH  - Neoplasms, Hormone-Dependent/*genetics
MH  - Nucleic Acid Hybridization
MH  - Prostatic Neoplasms/*genetics
MH  - Proto-Oncogene Proteins c-bcl-2/genetics
MH  - Proto-Oncogene Proteins c-myc/genetics
MH  - Receptors, Androgen/genetics
PMC - PMC1852946
EDAT- 1998/07/17 00:00
MHDA- 1998/07/17 00:01
PMCR- 1999/01/01
CRDT- 1998/07/17 00:00
PHST- 1998/07/17 00:00 [pubmed]
PHST- 1998/07/17 00:01 [medline]
PHST- 1998/07/17 00:00 [entrez]
PHST- 1999/01/01 00:00 [pmc-release]
AID - S0002-9440(10)65554-X [pii]
AID - 1343 [pii]
AID - 10.1016/S0002-9440(10)65554-X [doi]
PST - ppublish
SO  - Am J Pathol. 1998 Jul;153(1):141-8. doi: 10.1016/S0002-9440(10)65554-X.