Deletion of the inhibitor of growth 4 (ING4) tumor suppressor gene is prevalent in human epidermal growth factor 2 (HER2)-positive breast cancer

Coya Tapia, Inti Zlobec, Sandra Schneider, Ergin Kilic, Uwe Güth, Lukas Bubendorf, Suwon Kim

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Inhibitor of growth 4 (ING4) is a candidate tumor suppressor gene that was shown to be deleted in 10% to 20% of breast cancers by array comparative genome hybridization analysis. We developed fluorescent in situ hybridization to detect the ING4 gene directly in the tissue samples on tumor tissue microarrays. We evaluated the ING4 gene status in 1033 breast cancer tissue samples and observed that ING4 was deleted in 16.5% (170/1033) of all breast cancers. ING4 deletion was significantly associated with Her2 overexpression: of the tumors with ING4 deletion, 23.8% (39/164) were human epidermal growth factor 2 (HER2) positive, as compared with 14.1% (115/814) of the tumors without ING4 deletion (P = .002). In addition, the tumors with ING4 deletion were more likely to belong to the HER2 molecular subtype (estrogen receptor negative/progesterone receptor negative/human epidermal growth factor positive) of breast cancer, compared with the other subtypes (28.4% HER2 versus 15.7% all, P = .002). ING4 deletion did not affect survival outcome of all patients with breast cancer (P = .797) or of the patients with HER2-positive tumors (P = .792). We conclude that ING4 deletion in breast cancer is relatively common, as 1 in 6 breast cancer harbors ING4 deletion. Furthermore, ING4 deletion is more prevalent in HER2-positive tumors, suggesting a functional antagonistic relationship between the ING4 tumor suppressor and the HER2 oncogene. These results sustain the view that ING4 is a tumor suppressor in breast cancer and suggest that ING4 deletion may contribute to the pathogenesis of HER2-positive breast cancer.

Original languageEnglish (US)
Pages (from-to)983-990
Number of pages8
JournalHuman Pathology
Volume42
Issue number7
DOIs
StatePublished - Jul 2011

Fingerprint

Growth Inhibitors
Tumor Suppressor Genes
Epidermal Growth Factor
Breast Neoplasms
Neoplasms
Comparative Genomic Hybridization
Progesterone Receptors
Fluorescence In Situ Hybridization
Oncogenes
Estrogen Receptors

Keywords

  • Breast cancer
  • FISH
  • HER2/neu
  • ING4
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Deletion of the inhibitor of growth 4 (ING4) tumor suppressor gene is prevalent in human epidermal growth factor 2 (HER2)-positive breast cancer. / Tapia, Coya; Zlobec, Inti; Schneider, Sandra; Kilic, Ergin; Güth, Uwe; Bubendorf, Lukas; Kim, Suwon.

In: Human Pathology, Vol. 42, No. 7, 07.2011, p. 983-990.

Research output: Contribution to journalArticle

Tapia, Coya ; Zlobec, Inti ; Schneider, Sandra ; Kilic, Ergin ; Güth, Uwe ; Bubendorf, Lukas ; Kim, Suwon. / Deletion of the inhibitor of growth 4 (ING4) tumor suppressor gene is prevalent in human epidermal growth factor 2 (HER2)-positive breast cancer. In: Human Pathology. 2011 ; Vol. 42, No. 7. pp. 983-990.
@article{252ef6bfc6634dcf90c54e5a512fe559,
title = "Deletion of the inhibitor of growth 4 (ING4) tumor suppressor gene is prevalent in human epidermal growth factor 2 (HER2)-positive breast cancer",
abstract = "Inhibitor of growth 4 (ING4) is a candidate tumor suppressor gene that was shown to be deleted in 10{\%} to 20{\%} of breast cancers by array comparative genome hybridization analysis. We developed fluorescent in situ hybridization to detect the ING4 gene directly in the tissue samples on tumor tissue microarrays. We evaluated the ING4 gene status in 1033 breast cancer tissue samples and observed that ING4 was deleted in 16.5{\%} (170/1033) of all breast cancers. ING4 deletion was significantly associated with Her2 overexpression: of the tumors with ING4 deletion, 23.8{\%} (39/164) were human epidermal growth factor 2 (HER2) positive, as compared with 14.1{\%} (115/814) of the tumors without ING4 deletion (P = .002). In addition, the tumors with ING4 deletion were more likely to belong to the HER2 molecular subtype (estrogen receptor negative/progesterone receptor negative/human epidermal growth factor positive) of breast cancer, compared with the other subtypes (28.4{\%} HER2 versus 15.7{\%} all, P = .002). ING4 deletion did not affect survival outcome of all patients with breast cancer (P = .797) or of the patients with HER2-positive tumors (P = .792). We conclude that ING4 deletion in breast cancer is relatively common, as 1 in 6 breast cancer harbors ING4 deletion. Furthermore, ING4 deletion is more prevalent in HER2-positive tumors, suggesting a functional antagonistic relationship between the ING4 tumor suppressor and the HER2 oncogene. These results sustain the view that ING4 is a tumor suppressor in breast cancer and suggest that ING4 deletion may contribute to the pathogenesis of HER2-positive breast cancer.",
keywords = "Breast cancer, FISH, HER2/neu, ING4, Tumor suppressor gene",
author = "Coya Tapia and Inti Zlobec and Sandra Schneider and Ergin Kilic and Uwe G{\"u}th and Lukas Bubendorf and Suwon Kim",
year = "2011",
month = "7",
doi = "10.1016/j.humpath.2010.10.012",
language = "English (US)",
volume = "42",
pages = "983--990",
journal = "Human Pathology",
issn = "0046-8177",
publisher = "W.B. Saunders Ltd",
number = "7",

}

TY - JOUR

T1 - Deletion of the inhibitor of growth 4 (ING4) tumor suppressor gene is prevalent in human epidermal growth factor 2 (HER2)-positive breast cancer

AU - Tapia, Coya

AU - Zlobec, Inti

AU - Schneider, Sandra

AU - Kilic, Ergin

AU - Güth, Uwe

AU - Bubendorf, Lukas

AU - Kim, Suwon

PY - 2011/7

Y1 - 2011/7

N2 - Inhibitor of growth 4 (ING4) is a candidate tumor suppressor gene that was shown to be deleted in 10% to 20% of breast cancers by array comparative genome hybridization analysis. We developed fluorescent in situ hybridization to detect the ING4 gene directly in the tissue samples on tumor tissue microarrays. We evaluated the ING4 gene status in 1033 breast cancer tissue samples and observed that ING4 was deleted in 16.5% (170/1033) of all breast cancers. ING4 deletion was significantly associated with Her2 overexpression: of the tumors with ING4 deletion, 23.8% (39/164) were human epidermal growth factor 2 (HER2) positive, as compared with 14.1% (115/814) of the tumors without ING4 deletion (P = .002). In addition, the tumors with ING4 deletion were more likely to belong to the HER2 molecular subtype (estrogen receptor negative/progesterone receptor negative/human epidermal growth factor positive) of breast cancer, compared with the other subtypes (28.4% HER2 versus 15.7% all, P = .002). ING4 deletion did not affect survival outcome of all patients with breast cancer (P = .797) or of the patients with HER2-positive tumors (P = .792). We conclude that ING4 deletion in breast cancer is relatively common, as 1 in 6 breast cancer harbors ING4 deletion. Furthermore, ING4 deletion is more prevalent in HER2-positive tumors, suggesting a functional antagonistic relationship between the ING4 tumor suppressor and the HER2 oncogene. These results sustain the view that ING4 is a tumor suppressor in breast cancer and suggest that ING4 deletion may contribute to the pathogenesis of HER2-positive breast cancer.

AB - Inhibitor of growth 4 (ING4) is a candidate tumor suppressor gene that was shown to be deleted in 10% to 20% of breast cancers by array comparative genome hybridization analysis. We developed fluorescent in situ hybridization to detect the ING4 gene directly in the tissue samples on tumor tissue microarrays. We evaluated the ING4 gene status in 1033 breast cancer tissue samples and observed that ING4 was deleted in 16.5% (170/1033) of all breast cancers. ING4 deletion was significantly associated with Her2 overexpression: of the tumors with ING4 deletion, 23.8% (39/164) were human epidermal growth factor 2 (HER2) positive, as compared with 14.1% (115/814) of the tumors without ING4 deletion (P = .002). In addition, the tumors with ING4 deletion were more likely to belong to the HER2 molecular subtype (estrogen receptor negative/progesterone receptor negative/human epidermal growth factor positive) of breast cancer, compared with the other subtypes (28.4% HER2 versus 15.7% all, P = .002). ING4 deletion did not affect survival outcome of all patients with breast cancer (P = .797) or of the patients with HER2-positive tumors (P = .792). We conclude that ING4 deletion in breast cancer is relatively common, as 1 in 6 breast cancer harbors ING4 deletion. Furthermore, ING4 deletion is more prevalent in HER2-positive tumors, suggesting a functional antagonistic relationship between the ING4 tumor suppressor and the HER2 oncogene. These results sustain the view that ING4 is a tumor suppressor in breast cancer and suggest that ING4 deletion may contribute to the pathogenesis of HER2-positive breast cancer.

KW - Breast cancer

KW - FISH

KW - HER2/neu

KW - ING4

KW - Tumor suppressor gene

UR - http://www.scopus.com/inward/record.url?scp=79959356720&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79959356720&partnerID=8YFLogxK

U2 - 10.1016/j.humpath.2010.10.012

DO - 10.1016/j.humpath.2010.10.012

M3 - Article

C2 - 21315418

AN - SCOPUS:79959356720

VL - 42

SP - 983

EP - 990

JO - Human Pathology

JF - Human Pathology

SN - 0046-8177

IS - 7

ER -