Allelic imbalance in the clonal evolution of prostate carcinoma

Liang Cheng, David G. Bostwick, Guang Li, Quanhong Wang, Nan Hu, Alexander Vortmeyer, Zhengping Zhuang

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2017-2022
Number of pages6
JournalCancer
Volume85
Issue number9
DOIs
StatePublished - May 1 1999

Fingerprint

Allelic Imbalance
Clonal Evolution
Prostate
Carcinoma
Loss of Heterozygosity
Neoplasms
Neoplasm Metastasis
Genetic Markers
Chromosomes
Lymph Nodes
Alleles
BRCA1 Gene
Chromosomes, Human, Pair 21
Microdissection
Surgical Pathology
DNA Primers
Genetic Heterogeneity
Prostatectomy
Lymph Node Excision
Microsatellite Repeats

Keywords

  • Allelic imbalance
  • Metastases
  • Microdissection
  • Progression
  • Prostate

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Allelic imbalance in the clonal evolution of prostate carcinoma. / Cheng, Liang; Bostwick, David G.; Li, Guang; Wang, Quanhong; Hu, Nan; Vortmeyer, Alexander; Zhuang, Zhengping.

In: Cancer, Vol. 85, No. 9, 01.05.1999, p. 2017-2022.

Research output: Contribution to journalArticle

Cheng, Liang ; Bostwick, David G. ; Li, Guang ; Wang, Quanhong ; Hu, Nan ; Vortmeyer, Alexander ; Zhuang, Zhengping. / Allelic imbalance in the clonal evolution of prostate carcinoma. In: Cancer. 1999 ; Vol. 85, No. 9. pp. 2017-2022.
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title = "Allelic imbalance in the clonal evolution of prostate carcinoma",
abstract = "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.",
keywords = "Allelic imbalance, Metastases, Microdissection, Progression, Prostate",
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T1 - Allelic imbalance in the clonal evolution of prostate carcinoma

AU - Cheng, Liang

AU - Bostwick, David G.

AU - Li, Guang

AU - Wang, Quanhong

AU - Hu, Nan

AU - Vortmeyer, Alexander

AU - Zhuang, Zhengping

PY - 1999/5/1

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N2 - 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.

AB - 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.

KW - Allelic imbalance

KW - Metastases

KW - Microdissection

KW - Progression

KW - Prostate

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