Aberrant methylation of HIN-1 (high in normal-1) is a frequent event in many human malignancies

Hisayuki Shigematsu, Makoto Suzuki, Takao Takahashi, Kuniharu Miyajima, Shinichi Toyooka, Narayan Shivapurkar, Gail E. Tomlinson, Domenico Mastrangelo, Harvey I. Pass, Elisabeth Brambilla, Ubaradka G. Sathyanarayana, Bogdan Czerniak, Takehiko Fujisawa, Nobuyoshi Shimizu, Adi F. Gazdar

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

HIN-1 (high in normal-1) is a putative cytokine with growth inhibitory activities and is downregulated by aberrant methylation in breast cancers. We studied HIN-1 methylation status in many types of adult and pediatric malignancies and cell lines. We examined the expression of HIN-1 mRNA in 52 cell lines and the promoter methylation status in the cell lines and in over 800 primary tumors representing 17 tumor types using methylation specific PCR. Promoter methylation was observed in 73% of breast cancer, 67% of nonsmall cell lung cancer (NSCLC), 30% of small cell lung cancer (SCLC) and 57% of malignant mesothelioma (MM) cell lines, and methylation was completely correlated with loss of expression. Expression negative cell lines restored HIN-1 expression after treatment with 5-aza-2′-deoxycytidine. Promoter methylation of HIN-1 was found in 90% of retinoblastomas, 73% of Wilms' tumors, 61% of rhabdomyosarcomas, 57% of breast cancers, 52% of prostate cancers, 40% of MMs, 28% of NSCLCs and 27% of lymphomas. Methylation frequencies in colorectal cancers, cervical cancers, bronchial carcinoids, SCLCs, neuroblastomas, osteosarcomas, leukemia, medulloblastomas and bladder cancers were lower (4-21%), while hepatoblastomas lacked methylation. HIN-1 methylation was rarely detected in nonmalignant tissues (8 of 165, 5%). Aberrant methylation of HIN-1 with loss of expression is a common event and may contribute to the pathogenesis of many types of human malignancies.

Original languageEnglish (US)
Pages (from-to)600-604
Number of pages5
JournalInternational Journal of Cancer
Volume113
Issue number4
DOIs
StatePublished - Feb 10 2005

Fingerprint

Methylation
Neoplasms
Cell Line
decitabine
Breast Neoplasms
Prostatic Neoplasms
Hepatoblastoma
Medulloblastoma
Wilms Tumor
Rhabdomyosarcoma
Retinoblastoma
Small Cell Lung Carcinoma
Carcinoid Tumor
Osteosarcoma
Neuroblastoma
Urinary Bladder Neoplasms
Non-Small Cell Lung Carcinoma
Uterine Cervical Neoplasms
Colorectal Neoplasms
Lymphoma

Keywords

  • HIN-1
  • Human cancer
  • Methylation
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Shigematsu, H., Suzuki, M., Takahashi, T., Miyajima, K., Toyooka, S., Shivapurkar, N., ... Gazdar, A. F. (2005). Aberrant methylation of HIN-1 (high in normal-1) is a frequent event in many human malignancies. International Journal of Cancer, 113(4), 600-604. https://doi.org/10.1002/ijc.20622

Aberrant methylation of HIN-1 (high in normal-1) is a frequent event in many human malignancies. / Shigematsu, Hisayuki; Suzuki, Makoto; Takahashi, Takao; Miyajima, Kuniharu; Toyooka, Shinichi; Shivapurkar, Narayan; Tomlinson, Gail E.; Mastrangelo, Domenico; Pass, Harvey I.; Brambilla, Elisabeth; Sathyanarayana, Ubaradka G.; Czerniak, Bogdan; Fujisawa, Takehiko; Shimizu, Nobuyoshi; Gazdar, Adi F.

In: International Journal of Cancer, Vol. 113, No. 4, 10.02.2005, p. 600-604.

Research output: Contribution to journalArticle

Shigematsu, H, Suzuki, M, Takahashi, T, Miyajima, K, Toyooka, S, Shivapurkar, N, Tomlinson, GE, Mastrangelo, D, Pass, HI, Brambilla, E, Sathyanarayana, UG, Czerniak, B, Fujisawa, T, Shimizu, N & Gazdar, AF 2005, 'Aberrant methylation of HIN-1 (high in normal-1) is a frequent event in many human malignancies', International Journal of Cancer, vol. 113, no. 4, pp. 600-604. https://doi.org/10.1002/ijc.20622
Shigematsu H, Suzuki M, Takahashi T, Miyajima K, Toyooka S, Shivapurkar N et al. Aberrant methylation of HIN-1 (high in normal-1) is a frequent event in many human malignancies. International Journal of Cancer. 2005 Feb 10;113(4):600-604. https://doi.org/10.1002/ijc.20622
Shigematsu, Hisayuki ; Suzuki, Makoto ; Takahashi, Takao ; Miyajima, Kuniharu ; Toyooka, Shinichi ; Shivapurkar, Narayan ; Tomlinson, Gail E. ; Mastrangelo, Domenico ; Pass, Harvey I. ; Brambilla, Elisabeth ; Sathyanarayana, Ubaradka G. ; Czerniak, Bogdan ; Fujisawa, Takehiko ; Shimizu, Nobuyoshi ; Gazdar, Adi F. / Aberrant methylation of HIN-1 (high in normal-1) is a frequent event in many human malignancies. In: International Journal of Cancer. 2005 ; Vol. 113, No. 4. pp. 600-604.
@article{a0f34c6768d5492aacac8a146f96b5f2,
title = "Aberrant methylation of HIN-1 (high in normal-1) is a frequent event in many human malignancies",
abstract = "HIN-1 (high in normal-1) is a putative cytokine with growth inhibitory activities and is downregulated by aberrant methylation in breast cancers. We studied HIN-1 methylation status in many types of adult and pediatric malignancies and cell lines. We examined the expression of HIN-1 mRNA in 52 cell lines and the promoter methylation status in the cell lines and in over 800 primary tumors representing 17 tumor types using methylation specific PCR. Promoter methylation was observed in 73{\%} of breast cancer, 67{\%} of nonsmall cell lung cancer (NSCLC), 30{\%} of small cell lung cancer (SCLC) and 57{\%} of malignant mesothelioma (MM) cell lines, and methylation was completely correlated with loss of expression. Expression negative cell lines restored HIN-1 expression after treatment with 5-aza-2′-deoxycytidine. Promoter methylation of HIN-1 was found in 90{\%} of retinoblastomas, 73{\%} of Wilms' tumors, 61{\%} of rhabdomyosarcomas, 57{\%} of breast cancers, 52{\%} of prostate cancers, 40{\%} of MMs, 28{\%} of NSCLCs and 27{\%} of lymphomas. Methylation frequencies in colorectal cancers, cervical cancers, bronchial carcinoids, SCLCs, neuroblastomas, osteosarcomas, leukemia, medulloblastomas and bladder cancers were lower (4-21{\%}), while hepatoblastomas lacked methylation. HIN-1 methylation was rarely detected in nonmalignant tissues (8 of 165, 5{\%}). Aberrant methylation of HIN-1 with loss of expression is a common event and may contribute to the pathogenesis of many types of human malignancies.",
keywords = "HIN-1, Human cancer, Methylation, Tumor suppressor gene",
author = "Hisayuki Shigematsu and Makoto Suzuki and Takao Takahashi and Kuniharu Miyajima and Shinichi Toyooka and Narayan Shivapurkar and Tomlinson, {Gail E.} and Domenico Mastrangelo and Pass, {Harvey I.} and Elisabeth Brambilla and Sathyanarayana, {Ubaradka G.} and Bogdan Czerniak and Takehiko Fujisawa and Nobuyoshi Shimizu and Gazdar, {Adi F.}",
year = "2005",
month = "2",
day = "10",
doi = "10.1002/ijc.20622",
language = "English (US)",
volume = "113",
pages = "600--604",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - Aberrant methylation of HIN-1 (high in normal-1) is a frequent event in many human malignancies

AU - Shigematsu, Hisayuki

AU - Suzuki, Makoto

AU - Takahashi, Takao

AU - Miyajima, Kuniharu

AU - Toyooka, Shinichi

AU - Shivapurkar, Narayan

AU - Tomlinson, Gail E.

AU - Mastrangelo, Domenico

AU - Pass, Harvey I.

AU - Brambilla, Elisabeth

AU - Sathyanarayana, Ubaradka G.

AU - Czerniak, Bogdan

AU - Fujisawa, Takehiko

AU - Shimizu, Nobuyoshi

AU - Gazdar, Adi F.

PY - 2005/2/10

Y1 - 2005/2/10

N2 - HIN-1 (high in normal-1) is a putative cytokine with growth inhibitory activities and is downregulated by aberrant methylation in breast cancers. We studied HIN-1 methylation status in many types of adult and pediatric malignancies and cell lines. We examined the expression of HIN-1 mRNA in 52 cell lines and the promoter methylation status in the cell lines and in over 800 primary tumors representing 17 tumor types using methylation specific PCR. Promoter methylation was observed in 73% of breast cancer, 67% of nonsmall cell lung cancer (NSCLC), 30% of small cell lung cancer (SCLC) and 57% of malignant mesothelioma (MM) cell lines, and methylation was completely correlated with loss of expression. Expression negative cell lines restored HIN-1 expression after treatment with 5-aza-2′-deoxycytidine. Promoter methylation of HIN-1 was found in 90% of retinoblastomas, 73% of Wilms' tumors, 61% of rhabdomyosarcomas, 57% of breast cancers, 52% of prostate cancers, 40% of MMs, 28% of NSCLCs and 27% of lymphomas. Methylation frequencies in colorectal cancers, cervical cancers, bronchial carcinoids, SCLCs, neuroblastomas, osteosarcomas, leukemia, medulloblastomas and bladder cancers were lower (4-21%), while hepatoblastomas lacked methylation. HIN-1 methylation was rarely detected in nonmalignant tissues (8 of 165, 5%). Aberrant methylation of HIN-1 with loss of expression is a common event and may contribute to the pathogenesis of many types of human malignancies.

AB - HIN-1 (high in normal-1) is a putative cytokine with growth inhibitory activities and is downregulated by aberrant methylation in breast cancers. We studied HIN-1 methylation status in many types of adult and pediatric malignancies and cell lines. We examined the expression of HIN-1 mRNA in 52 cell lines and the promoter methylation status in the cell lines and in over 800 primary tumors representing 17 tumor types using methylation specific PCR. Promoter methylation was observed in 73% of breast cancer, 67% of nonsmall cell lung cancer (NSCLC), 30% of small cell lung cancer (SCLC) and 57% of malignant mesothelioma (MM) cell lines, and methylation was completely correlated with loss of expression. Expression negative cell lines restored HIN-1 expression after treatment with 5-aza-2′-deoxycytidine. Promoter methylation of HIN-1 was found in 90% of retinoblastomas, 73% of Wilms' tumors, 61% of rhabdomyosarcomas, 57% of breast cancers, 52% of prostate cancers, 40% of MMs, 28% of NSCLCs and 27% of lymphomas. Methylation frequencies in colorectal cancers, cervical cancers, bronchial carcinoids, SCLCs, neuroblastomas, osteosarcomas, leukemia, medulloblastomas and bladder cancers were lower (4-21%), while hepatoblastomas lacked methylation. HIN-1 methylation was rarely detected in nonmalignant tissues (8 of 165, 5%). Aberrant methylation of HIN-1 with loss of expression is a common event and may contribute to the pathogenesis of many types of human malignancies.

KW - HIN-1

KW - Human cancer

KW - Methylation

KW - Tumor suppressor gene

UR - http://www.scopus.com/inward/record.url?scp=19944415836&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=19944415836&partnerID=8YFLogxK

U2 - 10.1002/ijc.20622

DO - 10.1002/ijc.20622

M3 - Article

C2 - 15472908

AN - SCOPUS:19944415836

VL - 113

SP - 600

EP - 604

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 4

ER -