Organ-wide telomeric status in diseased and disease-free prostatic tissues

Christopher M Heaphy, Trisha M. Fleet, Eric G. Treat, Sang Joon Lee, Anthony Y. Smith, Michael S. Davis, Jeffrey K. Griffith, Edgar G. Fischer, Marco Bisoffi

Research output: Contribution to journalArticle

Abstract

Background Telomere attrition occurs early in the development of prostatic adenocarcinoma. However, little is known about either telomere status in benign prostatic hyperplasia (BPH), or the spatial and organ-wide distribution of potential telomere aberrations throughout all areas of prostatic glands affected by cancer or BPH. Methods Slot blot titration assay was used to determine telomere DNA content (TC), a proxy for telomere length, in macrodissected tissue consisting of 54 normal samples from 5 disease-free prostates, 128 BPH samples from 4 non-cancerous prostates, and 45 tumor, 73 BPH, and 4 prostatic intraepithelial neoplasia (PIN) samples from 5 cancerous prostates. Results Compared to TC in normal prostate samples (n=54; TC mean=0.98), tumor samples displayed telomere attrition (n=45; TC mean=0.67). TC in PIN samples was similar to tumors. TC in BPH samples from cancerous prostates was similar to TC in tumors and also displayed telomere shortening (n=73; TC mean=0.76), whereas BPH samples from non-cancerous prostates displayed longer telomeres (n=128; TC mean=1.06). In prostates affected by adenocarcinoma, areas of potential telomere attrition occurred in histologically normal tissues through the entire gland. However, three-dimensional zoning revealed a pattern of increasing TC as a function of distance from the primary (index) tumor. Conclusions Spatial distributions of TC in prostate specimens indicate a complex "field effect" with varying contributions from both cancer and BPH. The observation that telomere length variations occur in fields of histologically normal tissues surrounding the tumor is of clinical importance, as it may have implications for the diagnosis and focal therapy of prostate cancer. Prostate 70: 1471-1479, 2010.

Original languageEnglish (US)
Pages (from-to)1471-1479
Number of pages9
JournalProstate
Volume70
Issue number13
DOIs
StatePublished - Sep 15 2010

Fingerprint

Prostatic Diseases
Telomere
Prostate
Prostatic Hyperplasia
DNA
Neoplasms
Prostatic Intraepithelial Neoplasia
Adenocarcinoma

Keywords

  • Benign prostatic hyperplasia
  • Field cancerization
  • Prostate cancer
  • Telomere alterations

ASJC Scopus subject areas

  • Urology
  • Oncology
  • Medicine(all)

Cite this

Heaphy, C. M., Fleet, T. M., Treat, E. G., Lee, S. J., Smith, A. Y., Davis, M. S., ... Bisoffi, M. (2010). Organ-wide telomeric status in diseased and disease-free prostatic tissues. Prostate, 70(13), 1471-1479. https://doi.org/10.1002/pros.21182

Organ-wide telomeric status in diseased and disease-free prostatic tissues. / Heaphy, Christopher M; Fleet, Trisha M.; Treat, Eric G.; Lee, Sang Joon; Smith, Anthony Y.; Davis, Michael S.; Griffith, Jeffrey K.; Fischer, Edgar G.; Bisoffi, Marco.

In: Prostate, Vol. 70, No. 13, 15.09.2010, p. 1471-1479.

Research output: Contribution to journalArticle

Heaphy, CM, Fleet, TM, Treat, EG, Lee, SJ, Smith, AY, Davis, MS, Griffith, JK, Fischer, EG & Bisoffi, M 2010, 'Organ-wide telomeric status in diseased and disease-free prostatic tissues', Prostate, vol. 70, no. 13, pp. 1471-1479. https://doi.org/10.1002/pros.21182
Heaphy CM, Fleet TM, Treat EG, Lee SJ, Smith AY, Davis MS et al. Organ-wide telomeric status in diseased and disease-free prostatic tissues. Prostate. 2010 Sep 15;70(13):1471-1479. https://doi.org/10.1002/pros.21182
Heaphy, Christopher M ; Fleet, Trisha M. ; Treat, Eric G. ; Lee, Sang Joon ; Smith, Anthony Y. ; Davis, Michael S. ; Griffith, Jeffrey K. ; Fischer, Edgar G. ; Bisoffi, Marco. / Organ-wide telomeric status in diseased and disease-free prostatic tissues. In: Prostate. 2010 ; Vol. 70, No. 13. pp. 1471-1479.
@article{f10b1bdd7119444f885ca19f127b2376,
title = "Organ-wide telomeric status in diseased and disease-free prostatic tissues",
abstract = "Background Telomere attrition occurs early in the development of prostatic adenocarcinoma. However, little is known about either telomere status in benign prostatic hyperplasia (BPH), or the spatial and organ-wide distribution of potential telomere aberrations throughout all areas of prostatic glands affected by cancer or BPH. Methods Slot blot titration assay was used to determine telomere DNA content (TC), a proxy for telomere length, in macrodissected tissue consisting of 54 normal samples from 5 disease-free prostates, 128 BPH samples from 4 non-cancerous prostates, and 45 tumor, 73 BPH, and 4 prostatic intraepithelial neoplasia (PIN) samples from 5 cancerous prostates. Results Compared to TC in normal prostate samples (n=54; TC mean=0.98), tumor samples displayed telomere attrition (n=45; TC mean=0.67). TC in PIN samples was similar to tumors. TC in BPH samples from cancerous prostates was similar to TC in tumors and also displayed telomere shortening (n=73; TC mean=0.76), whereas BPH samples from non-cancerous prostates displayed longer telomeres (n=128; TC mean=1.06). In prostates affected by adenocarcinoma, areas of potential telomere attrition occurred in histologically normal tissues through the entire gland. However, three-dimensional zoning revealed a pattern of increasing TC as a function of distance from the primary (index) tumor. Conclusions Spatial distributions of TC in prostate specimens indicate a complex {"}field effect{"} with varying contributions from both cancer and BPH. The observation that telomere length variations occur in fields of histologically normal tissues surrounding the tumor is of clinical importance, as it may have implications for the diagnosis and focal therapy of prostate cancer. Prostate 70: 1471-1479, 2010.",
keywords = "Benign prostatic hyperplasia, Field cancerization, Prostate cancer, Telomere alterations",
author = "Heaphy, {Christopher M} and Fleet, {Trisha M.} and Treat, {Eric G.} and Lee, {Sang Joon} and Smith, {Anthony Y.} and Davis, {Michael S.} and Griffith, {Jeffrey K.} and Fischer, {Edgar G.} and Marco Bisoffi",
year = "2010",
month = "9",
day = "15",
doi = "10.1002/pros.21182",
language = "English (US)",
volume = "70",
pages = "1471--1479",
journal = "Prostate",
issn = "0270-4137",
publisher = "Wiley-Liss Inc.",
number = "13",

}

TY - JOUR

T1 - Organ-wide telomeric status in diseased and disease-free prostatic tissues

AU - Heaphy, Christopher M

AU - Fleet, Trisha M.

AU - Treat, Eric G.

AU - Lee, Sang Joon

AU - Smith, Anthony Y.

AU - Davis, Michael S.

AU - Griffith, Jeffrey K.

AU - Fischer, Edgar G.

AU - Bisoffi, Marco

PY - 2010/9/15

Y1 - 2010/9/15

N2 - Background Telomere attrition occurs early in the development of prostatic adenocarcinoma. However, little is known about either telomere status in benign prostatic hyperplasia (BPH), or the spatial and organ-wide distribution of potential telomere aberrations throughout all areas of prostatic glands affected by cancer or BPH. Methods Slot blot titration assay was used to determine telomere DNA content (TC), a proxy for telomere length, in macrodissected tissue consisting of 54 normal samples from 5 disease-free prostates, 128 BPH samples from 4 non-cancerous prostates, and 45 tumor, 73 BPH, and 4 prostatic intraepithelial neoplasia (PIN) samples from 5 cancerous prostates. Results Compared to TC in normal prostate samples (n=54; TC mean=0.98), tumor samples displayed telomere attrition (n=45; TC mean=0.67). TC in PIN samples was similar to tumors. TC in BPH samples from cancerous prostates was similar to TC in tumors and also displayed telomere shortening (n=73; TC mean=0.76), whereas BPH samples from non-cancerous prostates displayed longer telomeres (n=128; TC mean=1.06). In prostates affected by adenocarcinoma, areas of potential telomere attrition occurred in histologically normal tissues through the entire gland. However, three-dimensional zoning revealed a pattern of increasing TC as a function of distance from the primary (index) tumor. Conclusions Spatial distributions of TC in prostate specimens indicate a complex "field effect" with varying contributions from both cancer and BPH. The observation that telomere length variations occur in fields of histologically normal tissues surrounding the tumor is of clinical importance, as it may have implications for the diagnosis and focal therapy of prostate cancer. Prostate 70: 1471-1479, 2010.

AB - Background Telomere attrition occurs early in the development of prostatic adenocarcinoma. However, little is known about either telomere status in benign prostatic hyperplasia (BPH), or the spatial and organ-wide distribution of potential telomere aberrations throughout all areas of prostatic glands affected by cancer or BPH. Methods Slot blot titration assay was used to determine telomere DNA content (TC), a proxy for telomere length, in macrodissected tissue consisting of 54 normal samples from 5 disease-free prostates, 128 BPH samples from 4 non-cancerous prostates, and 45 tumor, 73 BPH, and 4 prostatic intraepithelial neoplasia (PIN) samples from 5 cancerous prostates. Results Compared to TC in normal prostate samples (n=54; TC mean=0.98), tumor samples displayed telomere attrition (n=45; TC mean=0.67). TC in PIN samples was similar to tumors. TC in BPH samples from cancerous prostates was similar to TC in tumors and also displayed telomere shortening (n=73; TC mean=0.76), whereas BPH samples from non-cancerous prostates displayed longer telomeres (n=128; TC mean=1.06). In prostates affected by adenocarcinoma, areas of potential telomere attrition occurred in histologically normal tissues through the entire gland. However, three-dimensional zoning revealed a pattern of increasing TC as a function of distance from the primary (index) tumor. Conclusions Spatial distributions of TC in prostate specimens indicate a complex "field effect" with varying contributions from both cancer and BPH. The observation that telomere length variations occur in fields of histologically normal tissues surrounding the tumor is of clinical importance, as it may have implications for the diagnosis and focal therapy of prostate cancer. Prostate 70: 1471-1479, 2010.

KW - Benign prostatic hyperplasia

KW - Field cancerization

KW - Prostate cancer

KW - Telomere alterations

UR - http://www.scopus.com/inward/record.url?scp=77956627409&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956627409&partnerID=8YFLogxK

U2 - 10.1002/pros.21182

DO - 10.1002/pros.21182

M3 - Article

C2 - 20687220

AN - SCOPUS:77956627409

VL - 70

SP - 1471

EP - 1479

JO - Prostate

JF - Prostate

SN - 0270-4137

IS - 13

ER -