Identification of 5 novel genes methylated in breast and other epithelial cancers

Victoria K. Hill, Luke B. Hesson, Temuujin Dansranjavin, Ashraf Dallol, Ivan Bieche, Sophie Vacher, Stella Tommasi, Timothy Dobbins, Dean Gentle, David Euhus, Cheryl Lewis, Reinhard Dammann, Robyn L. Ward, John Minna, Eammon R. Maher, Gerd P. Pfeifer, Farida Latif

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Background: There are several high throughput approaches to identify methylated genes in cancer. We utilized one such recently developed approach, MIRA (methylated-CpG island recovery assay) combined with CpG island arrays to identify novel genes that are epigenetically inactivated in breast cancer.Results: Using this approach we identified numerous CpG islands that demonstrated aberrant DNA methylation in breast cancer cell lines. Using a combination of COBRA and sequencing of bisulphite modified DNA, we confirmed 5 novel genes frequently methylated in breast tumours; EMILIN2, SALL1, DBC1, FBLN2 and CIDE-A. Methylation frequencies ranged from between 25% and 63% in primary breast tumours, whilst matched normal breast tissue DNA was either unmethylated or demonstrated a much lower frequency of methylation compared to malignant breast tissue DNA. Furthermore expression of the above 5 genes was shown to be restored following treatment with a demethylating agent in methylated breast cancer cell lines. We have expanded this analysis across three other common epithelial cancers (lung, colorectal, prostate). We demonstrate that the above genes show varying levels of methylation in these cancers. Lastly and most importantly methylation of EMILIN2 was associated with poorer clinical outcome in breast cancer and was strongly associated with estrogen receptor as well as progesterone receptor positive breast cancers.Conclusion: The combination of the MIRA assay with CpG island arrays is a very useful technique for identifying epigenetically inactivated genes in cancer genomes and can provide molecular markers for early cancer diagnosis, prognosis and epigenetic therapy.

Original languageEnglish (US)
Article number51
JournalMolecular Cancer
Volume9
DOIs
StatePublished - Mar 5 2010

Fingerprint

CpG Islands
Breast
Breast Neoplasms
Methylation
Genes
Neoplasms
Neoplasm Genes
DNA
Cell Line
Progesterone Receptors
DNA Methylation
Early Detection of Cancer
Epigenomics
Estrogen Receptors
Prostate
Lung Neoplasms
Genome

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology

Cite this

Hill, V. K., Hesson, L. B., Dansranjavin, T., Dallol, A., Bieche, I., Vacher, S., ... Latif, F. (2010). Identification of 5 novel genes methylated in breast and other epithelial cancers. Molecular Cancer, 9, [51]. https://doi.org/10.1186/1476-4598-9-51

Identification of 5 novel genes methylated in breast and other epithelial cancers. / Hill, Victoria K.; Hesson, Luke B.; Dansranjavin, Temuujin; Dallol, Ashraf; Bieche, Ivan; Vacher, Sophie; Tommasi, Stella; Dobbins, Timothy; Gentle, Dean; Euhus, David; Lewis, Cheryl; Dammann, Reinhard; Ward, Robyn L.; Minna, John; Maher, Eammon R.; Pfeifer, Gerd P.; Latif, Farida.

In: Molecular Cancer, Vol. 9, 51, 05.03.2010.

Research output: Contribution to journalArticle

Hill, VK, Hesson, LB, Dansranjavin, T, Dallol, A, Bieche, I, Vacher, S, Tommasi, S, Dobbins, T, Gentle, D, Euhus, D, Lewis, C, Dammann, R, Ward, RL, Minna, J, Maher, ER, Pfeifer, GP & Latif, F 2010, 'Identification of 5 novel genes methylated in breast and other epithelial cancers', Molecular Cancer, vol. 9, 51. https://doi.org/10.1186/1476-4598-9-51
Hill VK, Hesson LB, Dansranjavin T, Dallol A, Bieche I, Vacher S et al. Identification of 5 novel genes methylated in breast and other epithelial cancers. Molecular Cancer. 2010 Mar 5;9. 51. https://doi.org/10.1186/1476-4598-9-51
Hill, Victoria K. ; Hesson, Luke B. ; Dansranjavin, Temuujin ; Dallol, Ashraf ; Bieche, Ivan ; Vacher, Sophie ; Tommasi, Stella ; Dobbins, Timothy ; Gentle, Dean ; Euhus, David ; Lewis, Cheryl ; Dammann, Reinhard ; Ward, Robyn L. ; Minna, John ; Maher, Eammon R. ; Pfeifer, Gerd P. ; Latif, Farida. / Identification of 5 novel genes methylated in breast and other epithelial cancers. In: Molecular Cancer. 2010 ; Vol. 9.
@article{45b0c1f9ed534efab57109c8916a4cff,
title = "Identification of 5 novel genes methylated in breast and other epithelial cancers",
abstract = "Background: There are several high throughput approaches to identify methylated genes in cancer. We utilized one such recently developed approach, MIRA (methylated-CpG island recovery assay) combined with CpG island arrays to identify novel genes that are epigenetically inactivated in breast cancer.Results: Using this approach we identified numerous CpG islands that demonstrated aberrant DNA methylation in breast cancer cell lines. Using a combination of COBRA and sequencing of bisulphite modified DNA, we confirmed 5 novel genes frequently methylated in breast tumours; EMILIN2, SALL1, DBC1, FBLN2 and CIDE-A. Methylation frequencies ranged from between 25{\%} and 63{\%} in primary breast tumours, whilst matched normal breast tissue DNA was either unmethylated or demonstrated a much lower frequency of methylation compared to malignant breast tissue DNA. Furthermore expression of the above 5 genes was shown to be restored following treatment with a demethylating agent in methylated breast cancer cell lines. We have expanded this analysis across three other common epithelial cancers (lung, colorectal, prostate). We demonstrate that the above genes show varying levels of methylation in these cancers. Lastly and most importantly methylation of EMILIN2 was associated with poorer clinical outcome in breast cancer and was strongly associated with estrogen receptor as well as progesterone receptor positive breast cancers.Conclusion: The combination of the MIRA assay with CpG island arrays is a very useful technique for identifying epigenetically inactivated genes in cancer genomes and can provide molecular markers for early cancer diagnosis, prognosis and epigenetic therapy.",
author = "Hill, {Victoria K.} and Hesson, {Luke B.} and Temuujin Dansranjavin and Ashraf Dallol and Ivan Bieche and Sophie Vacher and Stella Tommasi and Timothy Dobbins and Dean Gentle and David Euhus and Cheryl Lewis and Reinhard Dammann and Ward, {Robyn L.} and John Minna and Maher, {Eammon R.} and Pfeifer, {Gerd P.} and Farida Latif",
year = "2010",
month = "3",
day = "5",
doi = "10.1186/1476-4598-9-51",
language = "English (US)",
volume = "9",
journal = "Molecular Cancer",
issn = "1476-4598",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Identification of 5 novel genes methylated in breast and other epithelial cancers

AU - Hill, Victoria K.

AU - Hesson, Luke B.

AU - Dansranjavin, Temuujin

AU - Dallol, Ashraf

AU - Bieche, Ivan

AU - Vacher, Sophie

AU - Tommasi, Stella

AU - Dobbins, Timothy

AU - Gentle, Dean

AU - Euhus, David

AU - Lewis, Cheryl

AU - Dammann, Reinhard

AU - Ward, Robyn L.

AU - Minna, John

AU - Maher, Eammon R.

AU - Pfeifer, Gerd P.

AU - Latif, Farida

PY - 2010/3/5

Y1 - 2010/3/5

N2 - Background: There are several high throughput approaches to identify methylated genes in cancer. We utilized one such recently developed approach, MIRA (methylated-CpG island recovery assay) combined with CpG island arrays to identify novel genes that are epigenetically inactivated in breast cancer.Results: Using this approach we identified numerous CpG islands that demonstrated aberrant DNA methylation in breast cancer cell lines. Using a combination of COBRA and sequencing of bisulphite modified DNA, we confirmed 5 novel genes frequently methylated in breast tumours; EMILIN2, SALL1, DBC1, FBLN2 and CIDE-A. Methylation frequencies ranged from between 25% and 63% in primary breast tumours, whilst matched normal breast tissue DNA was either unmethylated or demonstrated a much lower frequency of methylation compared to malignant breast tissue DNA. Furthermore expression of the above 5 genes was shown to be restored following treatment with a demethylating agent in methylated breast cancer cell lines. We have expanded this analysis across three other common epithelial cancers (lung, colorectal, prostate). We demonstrate that the above genes show varying levels of methylation in these cancers. Lastly and most importantly methylation of EMILIN2 was associated with poorer clinical outcome in breast cancer and was strongly associated with estrogen receptor as well as progesterone receptor positive breast cancers.Conclusion: The combination of the MIRA assay with CpG island arrays is a very useful technique for identifying epigenetically inactivated genes in cancer genomes and can provide molecular markers for early cancer diagnosis, prognosis and epigenetic therapy.

AB - Background: There are several high throughput approaches to identify methylated genes in cancer. We utilized one such recently developed approach, MIRA (methylated-CpG island recovery assay) combined with CpG island arrays to identify novel genes that are epigenetically inactivated in breast cancer.Results: Using this approach we identified numerous CpG islands that demonstrated aberrant DNA methylation in breast cancer cell lines. Using a combination of COBRA and sequencing of bisulphite modified DNA, we confirmed 5 novel genes frequently methylated in breast tumours; EMILIN2, SALL1, DBC1, FBLN2 and CIDE-A. Methylation frequencies ranged from between 25% and 63% in primary breast tumours, whilst matched normal breast tissue DNA was either unmethylated or demonstrated a much lower frequency of methylation compared to malignant breast tissue DNA. Furthermore expression of the above 5 genes was shown to be restored following treatment with a demethylating agent in methylated breast cancer cell lines. We have expanded this analysis across three other common epithelial cancers (lung, colorectal, prostate). We demonstrate that the above genes show varying levels of methylation in these cancers. Lastly and most importantly methylation of EMILIN2 was associated with poorer clinical outcome in breast cancer and was strongly associated with estrogen receptor as well as progesterone receptor positive breast cancers.Conclusion: The combination of the MIRA assay with CpG island arrays is a very useful technique for identifying epigenetically inactivated genes in cancer genomes and can provide molecular markers for early cancer diagnosis, prognosis and epigenetic therapy.

UR - http://www.scopus.com/inward/record.url?scp=77950536708&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950536708&partnerID=8YFLogxK

U2 - 10.1186/1476-4598-9-51

DO - 10.1186/1476-4598-9-51

M3 - Article

VL - 9

JO - Molecular Cancer

JF - Molecular Cancer

SN - 1476-4598

M1 - 51

ER -