OPCML at 11q25 is epigenetically inactivated and has tumour suppressor function in epithelial ovarian cancer

G. C. Sellar, K. P. Watt, G. J. Rabiasz, E.A. Stronach, L. Li, E. P. Miller, C. E. Massie, J. Miller, B. Contreras-Moriera, Derek Scott, Iain Brown, A. R. Williams, P. A. Bates, J. F. Smyth, H. Gabra

Research output: Contribution to journalArticle

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Abstract

Epithelial ovarian cancer (EOC), the leading cause of death from gynecological malignancy, is a poorly understood disease. The typically advanced presentation of EOC with loco-regional dissemination in the peritoneal cavity and the rare incidence of visceral metastases are hallmarks of the disease. These features relate to the biology of the disease, which is a principal determinant of outcome(1,2). EOC arises as a result of genetic alterations sustained by the ovarian surface epithelium (OSE; ref. 3). The causes of these changes are unknown but are manifest by activation of oncogenes and inactivation of tumor-suppressor genes (TSGs). Our analysis of loss of heterozygosity at 11q25 identified OPCML (also called OBCAM), a member of the IgLON family of immunoglobulin (Ig) domain containing glycosylphosphatidylinositol (GPI)-anchored cell adhesion molecules, as a candidate TSG in EOC. OPCML is frequently somatically inactivated in EOC by allele loss and by CpG island methylation. OPCML has functional characteristics consistent with TSG properties both in vitro and in vivo. A somatic missense mutation from an individual with EOC shows clear evidence of loss of function. These findings suggest that OPCML is an excellent candidate for the 11q25 ovarian cancer TSG. This is the first description to our knowledge of the involvement of the IgLON family in cancer.

Original languageEnglish
Pages (from-to)337-343
Number of pages6
JournalNature Genetics
Volume34
DOIs
Publication statusPublished - 2003

Keywords

  • ADHESION MOLECULE OBCAM
  • CELL-ADHESION
  • HETEROPHILIC INTERACTIONS
  • NEURITE OUTGROWTH
  • RAT-BRAIN
  • EXPRESSION
  • HETEROZYGOSITY
  • PROTEIN
  • FAMILY
  • GENES

Cite this

Sellar, G. C., Watt, K. P., Rabiasz, G. J., Stronach, E. A., Li, L., Miller, E. P., ... Gabra, H. (2003). OPCML at 11q25 is epigenetically inactivated and has tumour suppressor function in epithelial ovarian cancer. Nature Genetics, 34, 337-343. https://doi.org/10.1038/ng1183

OPCML at 11q25 is epigenetically inactivated and has tumour suppressor function in epithelial ovarian cancer. / Sellar, G. C.; Watt, K. P.; Rabiasz, G. J.; Stronach, E.A.; Li, L.; Miller, E. P.; Massie, C. E.; Miller, J.; Contreras-Moriera, B.; Scott, Derek; Brown, Iain; Williams, A. R.; Bates, P. A.; Smyth, J. F.; Gabra, H.

In: Nature Genetics, Vol. 34, 2003, p. 337-343.

Research output: Contribution to journalArticle

Sellar, GC, Watt, KP, Rabiasz, GJ, Stronach, EA, Li, L, Miller, EP, Massie, CE, Miller, J, Contreras-Moriera, B, Scott, D, Brown, I, Williams, AR, Bates, PA, Smyth, JF & Gabra, H 2003, 'OPCML at 11q25 is epigenetically inactivated and has tumour suppressor function in epithelial ovarian cancer', Nature Genetics, vol. 34, pp. 337-343. https://doi.org/10.1038/ng1183
Sellar, G. C. ; Watt, K. P. ; Rabiasz, G. J. ; Stronach, E.A. ; Li, L. ; Miller, E. P. ; Massie, C. E. ; Miller, J. ; Contreras-Moriera, B. ; Scott, Derek ; Brown, Iain ; Williams, A. R. ; Bates, P. A. ; Smyth, J. F. ; Gabra, H. / OPCML at 11q25 is epigenetically inactivated and has tumour suppressor function in epithelial ovarian cancer. In: Nature Genetics. 2003 ; Vol. 34. pp. 337-343.
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abstract = "Epithelial ovarian cancer (EOC), the leading cause of death from gynecological malignancy, is a poorly understood disease. The typically advanced presentation of EOC with loco-regional dissemination in the peritoneal cavity and the rare incidence of visceral metastases are hallmarks of the disease. These features relate to the biology of the disease, which is a principal determinant of outcome(1,2). EOC arises as a result of genetic alterations sustained by the ovarian surface epithelium (OSE; ref. 3). The causes of these changes are unknown but are manifest by activation of oncogenes and inactivation of tumor-suppressor genes (TSGs). Our analysis of loss of heterozygosity at 11q25 identified OPCML (also called OBCAM), a member of the IgLON family of immunoglobulin (Ig) domain containing glycosylphosphatidylinositol (GPI)-anchored cell adhesion molecules, as a candidate TSG in EOC. OPCML is frequently somatically inactivated in EOC by allele loss and by CpG island methylation. OPCML has functional characteristics consistent with TSG properties both in vitro and in vivo. A somatic missense mutation from an individual with EOC shows clear evidence of loss of function. These findings suggest that OPCML is an excellent candidate for the 11q25 ovarian cancer TSG. This is the first description to our knowledge of the involvement of the IgLON family in cancer.",
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T1 - OPCML at 11q25 is epigenetically inactivated and has tumour suppressor function in epithelial ovarian cancer

AU - Sellar, G. C.

AU - Watt, K. P.

AU - Rabiasz, G. J.

AU - Stronach, E.A.

AU - Li, L.

AU - Miller, E. P.

AU - Massie, C. E.

AU - Miller, J.

AU - Contreras-Moriera, B.

AU - Scott, Derek

AU - Brown, Iain

AU - Williams, A. R.

AU - Bates, P. A.

AU - Smyth, J. F.

AU - Gabra, H.

PY - 2003

Y1 - 2003

N2 - Epithelial ovarian cancer (EOC), the leading cause of death from gynecological malignancy, is a poorly understood disease. The typically advanced presentation of EOC with loco-regional dissemination in the peritoneal cavity and the rare incidence of visceral metastases are hallmarks of the disease. These features relate to the biology of the disease, which is a principal determinant of outcome(1,2). EOC arises as a result of genetic alterations sustained by the ovarian surface epithelium (OSE; ref. 3). The causes of these changes are unknown but are manifest by activation of oncogenes and inactivation of tumor-suppressor genes (TSGs). Our analysis of loss of heterozygosity at 11q25 identified OPCML (also called OBCAM), a member of the IgLON family of immunoglobulin (Ig) domain containing glycosylphosphatidylinositol (GPI)-anchored cell adhesion molecules, as a candidate TSG in EOC. OPCML is frequently somatically inactivated in EOC by allele loss and by CpG island methylation. OPCML has functional characteristics consistent with TSG properties both in vitro and in vivo. A somatic missense mutation from an individual with EOC shows clear evidence of loss of function. These findings suggest that OPCML is an excellent candidate for the 11q25 ovarian cancer TSG. This is the first description to our knowledge of the involvement of the IgLON family in cancer.

AB - Epithelial ovarian cancer (EOC), the leading cause of death from gynecological malignancy, is a poorly understood disease. The typically advanced presentation of EOC with loco-regional dissemination in the peritoneal cavity and the rare incidence of visceral metastases are hallmarks of the disease. These features relate to the biology of the disease, which is a principal determinant of outcome(1,2). EOC arises as a result of genetic alterations sustained by the ovarian surface epithelium (OSE; ref. 3). The causes of these changes are unknown but are manifest by activation of oncogenes and inactivation of tumor-suppressor genes (TSGs). Our analysis of loss of heterozygosity at 11q25 identified OPCML (also called OBCAM), a member of the IgLON family of immunoglobulin (Ig) domain containing glycosylphosphatidylinositol (GPI)-anchored cell adhesion molecules, as a candidate TSG in EOC. OPCML is frequently somatically inactivated in EOC by allele loss and by CpG island methylation. OPCML has functional characteristics consistent with TSG properties both in vitro and in vivo. A somatic missense mutation from an individual with EOC shows clear evidence of loss of function. These findings suggest that OPCML is an excellent candidate for the 11q25 ovarian cancer TSG. This is the first description to our knowledge of the involvement of the IgLON family in cancer.

KW - ADHESION MOLECULE OBCAM

KW - CELL-ADHESION

KW - HETEROPHILIC INTERACTIONS

KW - NEURITE OUTGROWTH

KW - RAT-BRAIN

KW - EXPRESSION

KW - HETEROZYGOSITY

KW - PROTEIN

KW - FAMILY

KW - GENES

U2 - 10.1038/ng1183

DO - 10.1038/ng1183

M3 - Article

VL - 34

SP - 337

EP - 343

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

ER -