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Allelic imbalance in the clonal evolution of prostate carcinoma . BACKGROUND To understand better the genetic basis of the clonal evolution of prostate carcinoma , the authors analyzed the pattern of allelic loss in 25 matched primary and metastatic prostate tumors . METHODS Twenty-five cases were selected from the surgical pathology files of the Mayo Clinic from patients who had undergone radical retropubic prostatectomy and bilateral lymphadenectomy between 1987-1991 . All patients had regional lymph node metastases at the time of surgery . DNA samples for the analysis of allelic loss pattern were prepared from primary tumors and matched synchronous lymph node metastases by tissue microdissection . The oligonucleotide primer pairs for the microsatellite DNA markers were D8S133 , D8S136 , D8S137 , ANK1 on chromosome 8p12-21 , LPLTET on chromosome 8p22 , and D17S855 ( intragenic to the BRCA1 gene ) on chromosome 17q21 . One case was not informative at any of the loci tested and was excluded from further analysis . RESULTS The overall frequency of allelic imbalance was 79 % in primary tumors and 88 % in paired metastases . Of 24 informative cases , 14 patients ( 58 % ) showed the same pattern of allelic loss or retention in matched primary and metastatic tumors at all marker locus ; discordant allelic loss was observed in the remaining 10 patients ( 42 % ) . Four patients showed loss of the same allele at one or more marker loci in both primary and metastatic tumors , but discordant allelic loss was observed at other marker loci . Five patients showed allelic loss in at least one genetic marker in the metastatic tumor but not in its matched primary tumor . Five patients displayed loss of one allele at one or more marker loci in a primary tumor but not in the matched metastases . There was no significant difference in the frequency of allelic imbalance between primary and metastatic tumors at any marker analyzed ( P > 0.05 ) . CONCLUSIONS These data suggest that different patterns of allelic deletion may be acquired during cancer progression to metastases . The differences in genetic composition between primary prostate carcinoma and its metastases may be related to intrinsic cancer heterogeneity , overall genetic instability , and clonal divergence .
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Intervention_Surgical
radical retropubic prostatectomy
778
Intervention_Surgical
bilateral lymphadenectomy
779
Outcome_Physical
Allelic imbalance
780
Outcome_Physical
allelic loss
781
Outcome_Physical
allelic loss
782
Outcome_Physical
overall frequency of allelic imbalance
783
Outcome_Physical
allelic loss
784
Outcome_Physical
allelic loss
785
Outcome_Physical
allele
786
Outcome_Physical
allelic loss
787
Outcome_Physical
allelic loss
788
Outcome_Physical
loss of one allele
789
Outcome_Physical
frequency of allelic imbalance
790
Outcome_Physical
allelic deletion
791
Participant_Condition
prostate carcinoma
792
Participant_Sample-size
25
793
Participant_Condition
primary and metastatic prostate tumors .
794
Participant_Sample-size
Twenty-five
795
Participant_Condition
regional lymph node metastases
796
Participant_Sample-size
24