Homozygous deletions of CDKN2A caused by alternative mechanisms in various human cancer cell lines

Publication type:
Journal article
Metadata:
Autoren
  • S Raschke
  • V Balz
  • T Efferth
  • WA Schulz
  • AR Florl
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000225367900006&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1002/gcc.20119
eISSN
1098-2264
Externe Identifier
  • Clarivate Analytics Document Solution ID: 874RQ
  • PubMed Identifier: 15495191
ISSN
1045-2257
Ausgabe der Veröffentlichung
1
Zeitschrift
GENES CHROMOSOMES & CANCER
Paginierung
58 - 67
Datum der Veröffentlichung
2005
Status
Published
Titel
Homozygous deletions of <i>CDKN2A</i> caused by alternative mechanisms in various human cancer cell lines
Sub types
  • Article
Ausgabe der Zeitschrift
42

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:title>Abstract</jats:title><jats:p>The <jats:italic>CDKN2A</jats:italic> tumor‐suppressor locus on chromosome band 9p21, which encodes <jats:italic>p16</jats:italic><jats:sup><jats:italic>INK4A</jats:italic></jats:sup>, a negative regulator of cyclin‐dependent kinases, and <jats:italic>p14</jats:italic><jats:sup><jats:italic>ARF1</jats:italic></jats:sup>, an activator of <jats:italic>TP53</jats:italic>, is inactivated in many human cancers by point mutation, promoter hypermethylation, and, often, deletion. Homozygous deletions are unusually prevalent at this locus in very different human cancers. In the present study, we compared deletions in squamous cell carcinoma of the head and neck (SCCHN) cell lines to those in T‐cell acute lymphatic leukemia (T‐ALL), glioma, and bladder carcinoma (TCC) cell lines. Of 14 SCCHN lines, 10 showed homozygous deletions of <jats:italic>CDKN2A</jats:italic>, one displayed promoter hypermethylation with gene silencing, and one had a frameshift deletion in exon 2. Many deletion ends were in or proximal to the repetitive sequence clusters flanking the locus. Breakpoint junctions displayed variable microhomologies or insertions characteristic of DNA repair by nonhomologous end‐joining. In general, deletions were much smaller in SCCHN than in TCC and glioma. In T‐ALL, breakpoints were near consensus sites for recombination mediated by RAG (recombination activating genes) enzymes, and the structure of the junctions was consistent with this mechanism. We suggest that different mechanisms of <jats:italic>CDKN2A</jats:italic> deletion prevail in different human cancers. Aberrant RAG‐mediated recombination may be responsible in T‐ALL, and exuberant DNA repair by nonhomologous end‐joining is the likely prevailing mechanism in SCCHN, but a distinct mechanism in TCC and glioma remains to be elucidated. © 2004 Wiley‐Liss, Inc.</jats:p>
Autoren
  • Sascha Raschke
  • Vera Balz
  • Thomas Efferth
  • Wolfgang A Schulz
  • Andrea R Florl
DOI
10.1002/gcc.20119
eISSN
1098-2264
ISSN
1045-2257
Ausgabe der Veröffentlichung
1
Zeitschrift
Genes, Chromosomes and Cancer
Sprache
en
Online publication date
2004
Paginierung
58 - 67
Datum der Veröffentlichung
2005
Status
Published
Herausgeber
Wiley
Herausgeber URL
http://dx.doi.org/10.1002/gcc.20119
Datum der Datenerfassung
2023
Titel
Homozygous deletions of <i>CDKN2A</i> caused by alternative mechanisms in various human cancer cell lines
Ausgabe der Zeitschrift
42

Data source: Crossref

Abstract
The CDKN2A tumor-suppressor locus on chromosome band 9p21, which encodes p16(INK4A), a negative regulator of cyclin-dependent kinases, and p14(ARF1), an activator of TP53, is inactivated in many human cancers by point mutation, promoter hypermethylation, and, often, deletion. Homozygous deletions are unusually prevalent at this locus in very different human cancers. In the present study, we compared deletions in squamous cell carcinoma of the head and neck (SCCHN) cell lines to those in T-cell acute lymphatic leukemia (T-ALL), glioma, and bladder carcinoma (TCC) cell lines. Of 14 SCCHN lines, 10 showed homozygous deletions of CDKN2A, one displayed promoter hypermethylation with gene silencing, and one had a frameshift deletion in exon 2. Many deletion ends were in or proximal to the repetitive sequence clusters flanking the locus. Breakpoint junctions displayed variable microhomologies or insertions characteristic of DNA repair by nonhomologous end-joining. In general, deletions were much smaller in SCCHN than in TCC and glioma. In T-ALL, breakpoints were near consensus sites for recombination mediated by RAG (recombination activating genes) enzymes, and the structure of the junctions was consistent with this mechanism. We suggest that different mechanisms of CDKN2A deletion prevail in different human cancers. Aberrant RAG-mediated recombination may be responsible in T-ALL, and exuberant DNA repair by nonhomologous end-joining is the likely prevailing mechanism in SCCHN, but a distinct mechanism in TCC and glioma remains to be elucidated.
Addresses
  • Urologische Klinik, Heinrich-Heine-Universität, Düsseldorf, Germany.
Autoren
  • Sascha Raschke
  • Vera Balz
  • Thomas Efferth
  • Thomas Efferth
  • Wolfgang A Schulz
  • Andrea R Florl
DOI
10.1002/gcc.20119
eISSN
1098-2264
Externe Identifier
  • PubMed Identifier: 15495191
Open access
false
ISSN
1045-2257
Ausgabe der Veröffentlichung
1
Zeitschrift
Genes, chromosomes & cancer
Schlüsselwörter
  • Cell Line, Tumor
  • Chromosomes, Human, Pair 9
  • Humans
  • Neoplasms
  • RNA, Neoplasm
  • Reverse Transcriptase Polymerase Chain Reaction
  • Gene Deletion
  • Base Sequence
  • Homozygote
  • Genes, p16
  • Molecular Sequence Data
  • Cyclin-Dependent Kinase Inhibitor p16
Sprache
eng
Medium
Print
Paginierung
58 - 67
Datum der Veröffentlichung
2005
Status
Published
Datum der Datenerfassung
2004
Titel
Homozygous deletions of CDKN2A caused by alternative mechanisms in various human cancer cell lines.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
42

Data source: Europe PubMed Central

Abstract
The CDKN2A tumor-suppressor locus on chromosome band 9p21, which encodes p16(INK4A), a negative regulator of cyclin-dependent kinases, and p14(ARF1), an activator of TP53, is inactivated in many human cancers by point mutation, promoter hypermethylation, and, often, deletion. Homozygous deletions are unusually prevalent at this locus in very different human cancers. In the present study, we compared deletions in squamous cell carcinoma of the head and neck (SCCHN) cell lines to those in T-cell acute lymphatic leukemia (T-ALL), glioma, and bladder carcinoma (TCC) cell lines. Of 14 SCCHN lines, 10 showed homozygous deletions of CDKN2A, one displayed promoter hypermethylation with gene silencing, and one had a frameshift deletion in exon 2. Many deletion ends were in or proximal to the repetitive sequence clusters flanking the locus. Breakpoint junctions displayed variable microhomologies or insertions characteristic of DNA repair by nonhomologous end-joining. In general, deletions were much smaller in SCCHN than in TCC and glioma. In T-ALL, breakpoints were near consensus sites for recombination mediated by RAG (recombination activating genes) enzymes, and the structure of the junctions was consistent with this mechanism. We suggest that different mechanisms of CDKN2A deletion prevail in different human cancers. Aberrant RAG-mediated recombination may be responsible in T-ALL, and exuberant DNA repair by nonhomologous end-joining is the likely prevailing mechanism in SCCHN, but a distinct mechanism in TCC and glioma remains to be elucidated.
Autoren
  • Sascha Raschke
  • Vera Balz
  • Thomas Efferth
  • Wolfgang A Schulz
  • Andrea R Florl
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/15495191
DOI
10.1002/gcc.20119
ISSN
1045-2257
Ausgabe der Veröffentlichung
1
Zeitschrift
Genes Chromosomes Cancer
Schlüsselwörter
  • Base Sequence
  • Cell Line, Tumor
  • Chromosomes, Human, Pair 9
  • Cyclin-Dependent Kinase Inhibitor p16
  • Gene Deletion
  • Genes, p16
  • Homozygote
  • Humans
  • Molecular Sequence Data
  • Neoplasms
  • RNA, Neoplasm
  • Reverse Transcriptase Polymerase Chain Reaction
Sprache
eng
Country
United States
Paginierung
58 - 67
Datum der Veröffentlichung
2005
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2005
Titel
Homozygous deletions of CDKN2A caused by alternative mechanisms in various human cancer cell lines.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
42

Data source: PubMed

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