Evidence for alternative candidate genes near RB1 involved in clonal expansion of in situ urothelial neoplasia

Mi Sook Kim; Joon Jeong; Tadeusz Majewski; Andrzej Kram; Dong Sup Yoon; Ruo Dan Zhang; Jun Zhi Li; Konrad Ptaszynski; Tang C. Kuang; Jain Hua Zhou; Ubaradka G. Sathyanarayana; Tomasz Tuziak; Dennis A. Johnston; Herbert B. Grossman; Adi F. Gazdar; Steven E. Scherer; William F. Benedict; Bogdan Czerniak

doi:10.1038/labinvest.3700378

Evidence for alternative candidate genes near RB1 involved in clonal expansion of in situ urothelial neoplasia

Mi Sook Kim, Joon Jeong, Tadeusz Majewski, Andrzej Kram, Dong Sup Yoon, Ruo Dan Zhang, Jun Zhi Li, Konrad Ptaszynski, Tang C. Kuang, Jain Hua Zhou, Ubaradka G. Sathyanarayana, Tomasz Tuziak, Dennis A. Johnston, Herbert B. Grossman, Adi F. Gazdar, Steven E. Scherer, William F. Benedict, Bogdan Czerniak

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

In this paper, we present whole-organ histologic and genetic mapping studies using hypervariable DNA markers on chromosome 13 and then integrate the recombination- and single-nucleotide polymorphic sites (SNPs)-based deletion maps with the annotated genome sequence. Using bladders resected from patients with invasive urothelial carcinoma, we studied allelic patterns of 40 microsatellite markers mapping to all regions of chromosome 13 and 79 SNPs located within the 13q14 region containing the RB1 gene. A whole-organ histologic and genetic mapping strategy was used to identify the evolution of allelic losses on chromosome 13 during the progression of bladder neoplasia. Markers mapping to chromosomal regions involved in clonal expansion of preneoplastic intraurothelial lesions were subsequently tested in 25 tumors and 21 voided urine samples of patients with bladder cancer. Four clusters of allelic losses mapping to distinct regions of chromosome 13 were identified. Markers mapping to the 13q14 region that is flanked by D13S263 and D13S276, which contains the RB1 gene, showed allelic losses associated with early clonal expansion of intraurothelial neoplasia. Such losses could be identified in approximately 32% bladder tumor tissue samples and 38% of voided urines from patients with bladder cancer. The integration of distribution patterns of clonal allelic losses revealed by the microsatellite markers with those obtained by genotyping of SNPs disclosed that the loss within an approximately 4-Mb segment centered around RB1 may represent an incipient event in bladder neoplasia. However, the inactivation of RB1 occurred later and was associated with the onset of severe dysplasia/ carcinoma in situ. Our studies provide evidence for the presence of critical alternative candidate genes mapping to the 13q14 region that are involved in clonal expansion of neoplasia within the bladder antecedent to the inactivation of the RB1 gene.

Original language	English (US)
Pages (from-to)	175-190
Number of pages	16
Journal	Laboratory Investigation
Volume	86
Issue number	2
DOIs	https://doi.org/10.1038/labinvest.3700378
State	Published - Feb 2006

Keywords

Alternative candidate genes near RB1
Bladder in situ neoplasia
RB1 locus
SNP-based mapping
in situ neoplasia

ASJC Scopus subject areas

Pathology and Forensic Medicine
Molecular Biology
Cell Biology

Access to Document

10.1038/labinvest.3700378

Cite this

Kim, M. S., Jeong, J., Majewski, T., Kram, A., Yoon, D. S., Zhang, R. D., Li, J. Z., Ptaszynski, K., Kuang, T. C., Zhou, J. H., Sathyanarayana, U. G., Tuziak, T., Johnston, D. A., Grossman, H. B., Gazdar, A. F., Scherer, S. E., Benedict, W. F., & Czerniak, B. (2006). Evidence for alternative candidate genes near RB1 involved in clonal expansion of in situ urothelial neoplasia. Laboratory Investigation, 86(2), 175-190. https://doi.org/10.1038/labinvest.3700378

Kim, MS, Jeong, J, Majewski, T, Kram, A, Yoon, DS, Zhang, RD, Li, JZ, Ptaszynski, K, Kuang, TC, Zhou, JH, Sathyanarayana, UG, Tuziak, T, Johnston, DA, Grossman, HB, Gazdar, AF, Scherer, SE, Benedict, WF & Czerniak, B 2006, 'Evidence for alternative candidate genes near RB1 involved in clonal expansion of in situ urothelial neoplasia', Laboratory Investigation, vol. 86, no. 2, pp. 175-190. https://doi.org/10.1038/labinvest.3700378

@article{bf96e78046984222801d2182258085bc,

title = "Evidence for alternative candidate genes near RB1 involved in clonal expansion of in situ urothelial neoplasia",

abstract = "In this paper, we present whole-organ histologic and genetic mapping studies using hypervariable DNA markers on chromosome 13 and then integrate the recombination- and single-nucleotide polymorphic sites (SNPs)-based deletion maps with the annotated genome sequence. Using bladders resected from patients with invasive urothelial carcinoma, we studied allelic patterns of 40 microsatellite markers mapping to all regions of chromosome 13 and 79 SNPs located within the 13q14 region containing the RB1 gene. A whole-organ histologic and genetic mapping strategy was used to identify the evolution of allelic losses on chromosome 13 during the progression of bladder neoplasia. Markers mapping to chromosomal regions involved in clonal expansion of preneoplastic intraurothelial lesions were subsequently tested in 25 tumors and 21 voided urine samples of patients with bladder cancer. Four clusters of allelic losses mapping to distinct regions of chromosome 13 were identified. Markers mapping to the 13q14 region that is flanked by D13S263 and D13S276, which contains the RB1 gene, showed allelic losses associated with early clonal expansion of intraurothelial neoplasia. Such losses could be identified in approximately 32% bladder tumor tissue samples and 38% of voided urines from patients with bladder cancer. The integration of distribution patterns of clonal allelic losses revealed by the microsatellite markers with those obtained by genotyping of SNPs disclosed that the loss within an approximately 4-Mb segment centered around RB1 may represent an incipient event in bladder neoplasia. However, the inactivation of RB1 occurred later and was associated with the onset of severe dysplasia/ carcinoma in situ. Our studies provide evidence for the presence of critical alternative candidate genes mapping to the 13q14 region that are involved in clonal expansion of neoplasia within the bladder antecedent to the inactivation of the RB1 gene.",

keywords = "Alternative candidate genes near RB1, Bladder in situ neoplasia, RB1 locus, SNP-based mapping, in situ neoplasia",

author = "Kim, {Mi Sook} and Joon Jeong and Tadeusz Majewski and Andrzej Kram and Yoon, {Dong Sup} and Zhang, {Ruo Dan} and Li, {Jun Zhi} and Konrad Ptaszynski and Kuang, {Tang C.} and Zhou, {Jain Hua} and Sathyanarayana, {Ubaradka G.} and Tomasz Tuziak and Johnston, {Dennis A.} and Grossman, {Herbert B.} and Gazdar, {Adi F.} and Scherer, {Steven E.} and Benedict, {William F.} and Bogdan Czerniak",

note = "Funding Information: This work was supported by National Institute of Health Grants UO1 CA85078 (BC), R01 CA66723 (BC), and GU SPORE Grant P50 CA91846. We would like to thank Stephanie M Rodriguez for secretarial assistance and Sandra Ideker-Soule for computerized graphical design of figures.",

year = "2006",

month = feb,

doi = "10.1038/labinvest.3700378",

language = "English (US)",

volume = "86",

pages = "175--190",

journal = "Laboratory Investigation",

issn = "0023-6837",

publisher = "Nature Publishing Group",

number = "2",

}

TY - JOUR

T1 - Evidence for alternative candidate genes near RB1 involved in clonal expansion of in situ urothelial neoplasia

AU - Kim, Mi Sook

AU - Jeong, Joon

AU - Majewski, Tadeusz

AU - Kram, Andrzej

AU - Yoon, Dong Sup

AU - Zhang, Ruo Dan

AU - Li, Jun Zhi

AU - Ptaszynski, Konrad

AU - Kuang, Tang C.

AU - Zhou, Jain Hua

AU - Sathyanarayana, Ubaradka G.

AU - Tuziak, Tomasz

AU - Johnston, Dennis A.

AU - Grossman, Herbert B.

AU - Gazdar, Adi F.

AU - Scherer, Steven E.

AU - Benedict, William F.

AU - Czerniak, Bogdan

N1 - Funding Information: This work was supported by National Institute of Health Grants UO1 CA85078 (BC), R01 CA66723 (BC), and GU SPORE Grant P50 CA91846. We would like to thank Stephanie M Rodriguez for secretarial assistance and Sandra Ideker-Soule for computerized graphical design of figures.

PY - 2006/2

Y1 - 2006/2

N2 - In this paper, we present whole-organ histologic and genetic mapping studies using hypervariable DNA markers on chromosome 13 and then integrate the recombination- and single-nucleotide polymorphic sites (SNPs)-based deletion maps with the annotated genome sequence. Using bladders resected from patients with invasive urothelial carcinoma, we studied allelic patterns of 40 microsatellite markers mapping to all regions of chromosome 13 and 79 SNPs located within the 13q14 region containing the RB1 gene. A whole-organ histologic and genetic mapping strategy was used to identify the evolution of allelic losses on chromosome 13 during the progression of bladder neoplasia. Markers mapping to chromosomal regions involved in clonal expansion of preneoplastic intraurothelial lesions were subsequently tested in 25 tumors and 21 voided urine samples of patients with bladder cancer. Four clusters of allelic losses mapping to distinct regions of chromosome 13 were identified. Markers mapping to the 13q14 region that is flanked by D13S263 and D13S276, which contains the RB1 gene, showed allelic losses associated with early clonal expansion of intraurothelial neoplasia. Such losses could be identified in approximately 32% bladder tumor tissue samples and 38% of voided urines from patients with bladder cancer. The integration of distribution patterns of clonal allelic losses revealed by the microsatellite markers with those obtained by genotyping of SNPs disclosed that the loss within an approximately 4-Mb segment centered around RB1 may represent an incipient event in bladder neoplasia. However, the inactivation of RB1 occurred later and was associated with the onset of severe dysplasia/ carcinoma in situ. Our studies provide evidence for the presence of critical alternative candidate genes mapping to the 13q14 region that are involved in clonal expansion of neoplasia within the bladder antecedent to the inactivation of the RB1 gene.

AB - In this paper, we present whole-organ histologic and genetic mapping studies using hypervariable DNA markers on chromosome 13 and then integrate the recombination- and single-nucleotide polymorphic sites (SNPs)-based deletion maps with the annotated genome sequence. Using bladders resected from patients with invasive urothelial carcinoma, we studied allelic patterns of 40 microsatellite markers mapping to all regions of chromosome 13 and 79 SNPs located within the 13q14 region containing the RB1 gene. A whole-organ histologic and genetic mapping strategy was used to identify the evolution of allelic losses on chromosome 13 during the progression of bladder neoplasia. Markers mapping to chromosomal regions involved in clonal expansion of preneoplastic intraurothelial lesions were subsequently tested in 25 tumors and 21 voided urine samples of patients with bladder cancer. Four clusters of allelic losses mapping to distinct regions of chromosome 13 were identified. Markers mapping to the 13q14 region that is flanked by D13S263 and D13S276, which contains the RB1 gene, showed allelic losses associated with early clonal expansion of intraurothelial neoplasia. Such losses could be identified in approximately 32% bladder tumor tissue samples and 38% of voided urines from patients with bladder cancer. The integration of distribution patterns of clonal allelic losses revealed by the microsatellite markers with those obtained by genotyping of SNPs disclosed that the loss within an approximately 4-Mb segment centered around RB1 may represent an incipient event in bladder neoplasia. However, the inactivation of RB1 occurred later and was associated with the onset of severe dysplasia/ carcinoma in situ. Our studies provide evidence for the presence of critical alternative candidate genes mapping to the 13q14 region that are involved in clonal expansion of neoplasia within the bladder antecedent to the inactivation of the RB1 gene.

KW - Alternative candidate genes near RB1

KW - Bladder in situ neoplasia

KW - RB1 locus

KW - SNP-based mapping

KW - in situ neoplasia

UR - http://www.scopus.com/inward/record.url?scp=30944464247&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=30944464247&partnerID=8YFLogxK

U2 - 10.1038/labinvest.3700378

DO - 10.1038/labinvest.3700378

M3 - Article

C2 - 16402033

AN - SCOPUS:30944464247

SN - 0023-6837

VL - 86

SP - 175

EP - 190

JO - Laboratory Investigation

JF - Laboratory Investigation

IS - 2

ER -

Evidence for alternative candidate genes near RB1 involved in clonal expansion of in situ urothelial neoplasia

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this