Analysis of genetic and epigenetic processes that influence p14ARF expression in breast cancer

Javier Silva; Gemma Domínguez; José M. Silva; Jose M. García; Isabel Gallego; César Corbacho; Mariano Provencio; Pilar Espãa; Félix Bonilla

doi:10.1038/sj.onc.1204617

Analysis of genetic and epigenetic processes that influence p14ARF expression in breast cancer

Javier Silva, Gemma Domínguez, José M. Silva, Jose M. García, Isabel Gallego, César Corbacho, Mariano Provencio, Pilar Espãa, Félix Bonilla

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

45 Scopus citations

Abstract

The INK4a/ARF locus encodes two unrelated cell cycle-regulatory proteins that both function in tumor suppression, p16INK4a and p14ARF. In human tumors including breast cancer, alterations affecting selectively p14ARF have been poorly analysed. We have performed a comprehensive analysis of the inactivation mechanisms (mutation, homozygous and hemizygous deletion, and promoter hypermethylation) in a large series of 100 primary breast carcinomas. RT-PCR showed expression variable of the p14ARF transcript, with 17% demonstrating overexpression and 26% demonstrating decreased expression. No detectable alterations were observed in the majority of cases with overexpressed p14ARF mRNA, but 77% of tumors with decreased expression presented at least one of these genetic/epigenetic alterations. Nevertheless, a statistically significant correlation was observed between decreased p14ARF expression and several poor prognostic parameters.

Original language	English
Pages (from-to)	4586-4590
Number of pages	5
Journal	Oncogene
Volume	20
Issue number	33
DOIs	https://doi.org/10.1038/sj.onc.1204617
State	Published - 27 Jul 2001
Externally published	Yes

Keywords

Allelic losses
Breast cancer
Hypermethylation
Mutations
Overexpression
p14ARF

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10.1038/sj.onc.1204617

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@article{a3e228e75e9d493d88d05fbb5415ff8d,

title = "Analysis of genetic and epigenetic processes that influence p14ARF expression in breast cancer",

abstract = "The INK4a/ARF locus encodes two unrelated cell cycle-regulatory proteins that both function in tumor suppression, p16INK4a and p14ARF. In human tumors including breast cancer, alterations affecting selectively p14ARF have been poorly analysed. We have performed a comprehensive analysis of the inactivation mechanisms (mutation, homozygous and hemizygous deletion, and promoter hypermethylation) in a large series of 100 primary breast carcinomas. RT-PCR showed expression variable of the p14ARF transcript, with 17% demonstrating overexpression and 26% demonstrating decreased expression. No detectable alterations were observed in the majority of cases with overexpressed p14ARF mRNA, but 77% of tumors with decreased expression presented at least one of these genetic/epigenetic alterations. Nevertheless, a statistically significant correlation was observed between decreased p14ARF expression and several poor prognostic parameters.",

keywords = "Allelic losses, Breast cancer, Hypermethylation, Mutations, Overexpression, p14ARF",

author = "Javier Silva and Gemma Dom{\'i}nguez and Silva, {Jos{\'e} M.} and Garc{\'i}a, {Jose M.} and Isabel Gallego and C{\'e}sar Corbacho and Mariano Provencio and Pilar Esp{\~a}a and F{\'e}lix Bonilla",

note = "Funding Information: We are grateful to Mr Robin Rycroft for his assistance with the English language, revision and preparation of the manuscript. This work was supported by grants from the Fundaci{\'o}n Banco Santander Central Hispano, Aventis Pharma S.A and CAM 08.1/0069/20002.",

year = "2001",

month = jul,

day = "27",

doi = "10.1038/sj.onc.1204617",

language = "English",

volume = "20",

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journal = "Oncogene",

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T1 - Analysis of genetic and epigenetic processes that influence p14ARF expression in breast cancer

AU - Silva, Javier

AU - Domínguez, Gemma

AU - Silva, José M.

AU - García, Jose M.

AU - Gallego, Isabel

AU - Corbacho, César

AU - Provencio, Mariano

AU - Espãa, Pilar

AU - Bonilla, Félix

N1 - Funding Information: We are grateful to Mr Robin Rycroft for his assistance with the English language, revision and preparation of the manuscript. This work was supported by grants from the Fundación Banco Santander Central Hispano, Aventis Pharma S.A and CAM 08.1/0069/20002.

PY - 2001/7/27

Y1 - 2001/7/27

N2 - The INK4a/ARF locus encodes two unrelated cell cycle-regulatory proteins that both function in tumor suppression, p16INK4a and p14ARF. In human tumors including breast cancer, alterations affecting selectively p14ARF have been poorly analysed. We have performed a comprehensive analysis of the inactivation mechanisms (mutation, homozygous and hemizygous deletion, and promoter hypermethylation) in a large series of 100 primary breast carcinomas. RT-PCR showed expression variable of the p14ARF transcript, with 17% demonstrating overexpression and 26% demonstrating decreased expression. No detectable alterations were observed in the majority of cases with overexpressed p14ARF mRNA, but 77% of tumors with decreased expression presented at least one of these genetic/epigenetic alterations. Nevertheless, a statistically significant correlation was observed between decreased p14ARF expression and several poor prognostic parameters.

AB - The INK4a/ARF locus encodes two unrelated cell cycle-regulatory proteins that both function in tumor suppression, p16INK4a and p14ARF. In human tumors including breast cancer, alterations affecting selectively p14ARF have been poorly analysed. We have performed a comprehensive analysis of the inactivation mechanisms (mutation, homozygous and hemizygous deletion, and promoter hypermethylation) in a large series of 100 primary breast carcinomas. RT-PCR showed expression variable of the p14ARF transcript, with 17% demonstrating overexpression and 26% demonstrating decreased expression. No detectable alterations were observed in the majority of cases with overexpressed p14ARF mRNA, but 77% of tumors with decreased expression presented at least one of these genetic/epigenetic alterations. Nevertheless, a statistically significant correlation was observed between decreased p14ARF expression and several poor prognostic parameters.

KW - Allelic losses

KW - Breast cancer

KW - Hypermethylation

KW - Mutations

KW - Overexpression

KW - p14ARF

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U2 - 10.1038/sj.onc.1204617

DO - 10.1038/sj.onc.1204617

M3 - Article

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AN - SCOPUS:0035958571

SN - 0950-9232

VL - 20

SP - 4586

EP - 4590

JO - Oncogene

JF - Oncogene

IS - 33

ER -

Analysis of genetic and epigenetic processes that influence p14ARF expression in breast cancer

Abstract

Keywords

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