Oncogenic events associated with endometrial and ovarian cancers are rare in endometriosis.

TY - JOUR

T1 - Oncogenic events associated with endometrial and ovarian cancers are rare in endometriosis.

AU - Vestergaard, Anna Lindeløv

AU - Thorup, Katrine

AU - Knudsen, Ulla Breth

AU - Munk, Torben

AU - Rosbach, Hanne

AU - Poulsen, Jesper Buchhave

AU - Guldberg, Per

AU - Martensen, Pia Møller

PY - 2011

Y1 - 2011

N2 - Endometriosis displays some features that resemble malignant processes, including invasive growth, resistance to apoptosis, and distant implantation. The objective of this study was to investigate whether gene alterations that are frequent in endometrial and/or ovarian cancers contribute to the pathogenesis of endometriosis. Biopsies were obtained from ectopic endometriosis lesions from 23 patients with revised American Fertility Score (rAFS) stage 1 (N=1), 2 (N=10), 3 (N=11), or 4 (N=1) endometriosis. Six genes (APC, CDKN2A, PYCARD, RARB, RASSF1, and ESR1) were analyzed for promoter hypermethylation using methylation-specific melting curve analysis (MS-MCA), and 9 genes (BRAF, HRAS, NRAS, CTNNB1, CDK4, FGFR3, PIK3CA, TP53 and PTEN) were analyzed for mutations using denaturing gradient gel electrophoresis (DGGE) and direct sequencing. An oncogenic mutation in KRAS (c. 34G>T; p.G12C) was detected in a single lesion. No gene alterations were found in the remaining samples. Our data suggest that genetic and epigenetic events contributing to endometrial and ovarian cancers are rare in endometriosis. However, other proto-oncogenes and tumor suppressor genes should be tested for alterations in order to identify the molecular basis of the susceptibility of endometriosis to malignant transformation.

AB - Endometriosis displays some features that resemble malignant processes, including invasive growth, resistance to apoptosis, and distant implantation. The objective of this study was to investigate whether gene alterations that are frequent in endometrial and/or ovarian cancers contribute to the pathogenesis of endometriosis. Biopsies were obtained from ectopic endometriosis lesions from 23 patients with revised American Fertility Score (rAFS) stage 1 (N=1), 2 (N=10), 3 (N=11), or 4 (N=1) endometriosis. Six genes (APC, CDKN2A, PYCARD, RARB, RASSF1, and ESR1) were analyzed for promoter hypermethylation using methylation-specific melting curve analysis (MS-MCA), and 9 genes (BRAF, HRAS, NRAS, CTNNB1, CDK4, FGFR3, PIK3CA, TP53 and PTEN) were analyzed for mutations using denaturing gradient gel electrophoresis (DGGE) and direct sequencing. An oncogenic mutation in KRAS (c. 34G>T; p.G12C) was detected in a single lesion. No gene alterations were found in the remaining samples. Our data suggest that genetic and epigenetic events contributing to endometrial and ovarian cancers are rare in endometriosis. However, other proto-oncogenes and tumor suppressor genes should be tested for alterations in order to identify the molecular basis of the susceptibility of endometriosis to malignant transformation.

KW - endometriose

KW - endometrium

KW - malign

KW - mutation

KW - methylering

KW - endometriosis

KW - endometrium

KW - malignancy

KW - mutation

KW - methylation

U2 - 10.1093/molehr/gar049

DO - 10.1093/molehr/gar049

M3 - Journal article

C2 - 21724579

SN - 1360-9947

VL - 17

SP - 243

EP - 254

JO - Molecular Human Reproduction

JF - Molecular Human Reproduction

IS - 4

ER -