Regional DNA hypermethylation at D17S5 precedes 17p structural changes in the progression of renal tumors

Michele Makos, Barry D Nelkin, Stephen B Baylin, James R. Gnarra, James Brooks, William Isaacs, Marston Linehan, Stephen B. Baylin

Research output: Contribution to journalArticle

Abstract

In a preceding paper for brain tumors, we demonstrate a tight association between regional hypermethylation at locus D17S5 of chromosome 17p and allelic loss of this chromosome. Because 17p allelic losses occur at the earliest stages of brain tumors, the exact temporal relationship between this event and the hypermethylation could not be elucidated. In renal cancers, two linked structural changes on chromosome 17p, allelic loss and p53 gene mutations, generally occur late in progression. We now show that D17S5 hypermethylation is tightly coupled to both of these genetic changes in late stage renal tumors. However, the methylation change is the only one of the 17p abnormalities which occurs at a high incidence in early-stage renal cancers (hypermethylation, 50%; 17p allelic loss, 13%; p53 mutations, 0%). Our results firmly suggest that D17S5 regional hypermethylation precedes the appearance of the consistent 17p genetic changes in renal cancers, suggesting that this event either marks, or may even cause, chromatin changes which predispose to genetic instability.

Original languageEnglish (US)
Pages (from-to)2719-2722
Number of pages4
JournalCancer Research
Volume53
Issue number12
StatePublished - Jun 15 1993

Fingerprint

Loss of Heterozygosity
Kidney Neoplasms
Kidney
Chromosomes
DNA
Brain Neoplasms
Neoplasms
Mutation
p53 Genes
Methylation
Chromatin
Incidence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Regional DNA hypermethylation at D17S5 precedes 17p structural changes in the progression of renal tumors. / Makos, Michele; Nelkin, Barry D; Baylin, Stephen B; Gnarra, James R.; Brooks, James; Isaacs, William; Linehan, Marston; Baylin, Stephen B.

In: Cancer Research, Vol. 53, No. 12, 15.06.1993, p. 2719-2722.

Research output: Contribution to journalArticle

Makos, M, Nelkin, BD, Baylin, SB, Gnarra, JR, Brooks, J, Isaacs, W, Linehan, M & Baylin, SB 1993, 'Regional DNA hypermethylation at D17S5 precedes 17p structural changes in the progression of renal tumors', Cancer Research, vol. 53, no. 12, pp. 2719-2722.
Makos, Michele ; Nelkin, Barry D ; Baylin, Stephen B ; Gnarra, James R. ; Brooks, James ; Isaacs, William ; Linehan, Marston ; Baylin, Stephen B. / Regional DNA hypermethylation at D17S5 precedes 17p structural changes in the progression of renal tumors. In: Cancer Research. 1993 ; Vol. 53, No. 12. pp. 2719-2722.
@article{f3b9dd5df1484847b61c727ff0ef3cd8,
title = "Regional DNA hypermethylation at D17S5 precedes 17p structural changes in the progression of renal tumors",
abstract = "In a preceding paper for brain tumors, we demonstrate a tight association between regional hypermethylation at locus D17S5 of chromosome 17p and allelic loss of this chromosome. Because 17p allelic losses occur at the earliest stages of brain tumors, the exact temporal relationship between this event and the hypermethylation could not be elucidated. In renal cancers, two linked structural changes on chromosome 17p, allelic loss and p53 gene mutations, generally occur late in progression. We now show that D17S5 hypermethylation is tightly coupled to both of these genetic changes in late stage renal tumors. However, the methylation change is the only one of the 17p abnormalities which occurs at a high incidence in early-stage renal cancers (hypermethylation, 50{\%}; 17p allelic loss, 13{\%}; p53 mutations, 0{\%}). Our results firmly suggest that D17S5 regional hypermethylation precedes the appearance of the consistent 17p genetic changes in renal cancers, suggesting that this event either marks, or may even cause, chromatin changes which predispose to genetic instability.",
author = "Michele Makos and Nelkin, {Barry D} and Baylin, {Stephen B} and Gnarra, {James R.} and James Brooks and William Isaacs and Marston Linehan and Baylin, {Stephen B.}",
year = "1993",
month = "6",
day = "15",
language = "English (US)",
volume = "53",
pages = "2719--2722",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "12",

}

TY - JOUR

T1 - Regional DNA hypermethylation at D17S5 precedes 17p structural changes in the progression of renal tumors

AU - Makos, Michele

AU - Nelkin, Barry D

AU - Baylin, Stephen B

AU - Gnarra, James R.

AU - Brooks, James

AU - Isaacs, William

AU - Linehan, Marston

AU - Baylin, Stephen B.

PY - 1993/6/15

Y1 - 1993/6/15

N2 - In a preceding paper for brain tumors, we demonstrate a tight association between regional hypermethylation at locus D17S5 of chromosome 17p and allelic loss of this chromosome. Because 17p allelic losses occur at the earliest stages of brain tumors, the exact temporal relationship between this event and the hypermethylation could not be elucidated. In renal cancers, two linked structural changes on chromosome 17p, allelic loss and p53 gene mutations, generally occur late in progression. We now show that D17S5 hypermethylation is tightly coupled to both of these genetic changes in late stage renal tumors. However, the methylation change is the only one of the 17p abnormalities which occurs at a high incidence in early-stage renal cancers (hypermethylation, 50%; 17p allelic loss, 13%; p53 mutations, 0%). Our results firmly suggest that D17S5 regional hypermethylation precedes the appearance of the consistent 17p genetic changes in renal cancers, suggesting that this event either marks, or may even cause, chromatin changes which predispose to genetic instability.

AB - In a preceding paper for brain tumors, we demonstrate a tight association between regional hypermethylation at locus D17S5 of chromosome 17p and allelic loss of this chromosome. Because 17p allelic losses occur at the earliest stages of brain tumors, the exact temporal relationship between this event and the hypermethylation could not be elucidated. In renal cancers, two linked structural changes on chromosome 17p, allelic loss and p53 gene mutations, generally occur late in progression. We now show that D17S5 hypermethylation is tightly coupled to both of these genetic changes in late stage renal tumors. However, the methylation change is the only one of the 17p abnormalities which occurs at a high incidence in early-stage renal cancers (hypermethylation, 50%; 17p allelic loss, 13%; p53 mutations, 0%). Our results firmly suggest that D17S5 regional hypermethylation precedes the appearance of the consistent 17p genetic changes in renal cancers, suggesting that this event either marks, or may even cause, chromatin changes which predispose to genetic instability.

UR - http://www.scopus.com/inward/record.url?scp=0027207886&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027207886&partnerID=8YFLogxK

M3 - Article

C2 - 8504410

AN - SCOPUS:0027207886

VL - 53

SP - 2719

EP - 2722

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 12

ER -