Role of the Hedgehog/Patched Signaling Pathway in Oncogenesis: A New Polymorphism in the PTCH Gene in Ovarian Fibroma

Abstract

We compared the expression of target genes of Hedgehog/Patched signaling in ovarian fibromas and ovarian dermoids. We noted that high levels of SHH appear almost regularly, especially in dermoids, usually accompanied by increased expression of SMO. GLI overexpression does not coincide with that of PTCH. Loss of heterozygosity findings in the PTCH locus and increased expression of several genes in the pathway strongly suggest that the pathway is involved in both ovarian fibroma and dermoids.

The Patched gene is epigenetically regulated in ovarian dermoids and fibromas, but not in basocellular carcinomas

“…The expression data published previously (7,8) show moderately increased activities of various pathway genes. In particular, expression of GLI1 was not consistently increased in all samples, whereas almost all tumors showed some increase in both SHH and SMO expression (7,8) which might in general be compatible with the low malignant potential of the analyzed tumor types; although details of the expression pattern did not quite fit into the typical model of the pathway activation). A similar expression analysis was performed here on BCC samples, and the results collated with expression data for dermoids and fibromas are reviewed in Table II.…”

“…Due to similar expression levels of pathway genes, we have included ovarian dermoids in our more recent investigations of ovarian fibroma (7). The latter are very strongly associated with BCNS and therefore expected to be largely caused by PTCH alterations: the incidence of ovarian fibroma in the syndrome patients is several times greater than in the general female population, and this relative increase is comparable to or greater than that of BCCs, the most common syndrome neoplasia.…”

The Patched gene is epigenetically regulated in ovarian dermoids and fibromas, but not in basocellular carcinomas

“…The expression data published previously (7,8) show moderately increased activities of various pathway genes. In particular, expression of GLI1 was not consistently increased in all samples, whereas almost all tumors showed some increase in both SHH and SMO expression (7,8) which might in general be compatible with the low malignant potential of the analyzed tumor types; although details of the expression pattern did not quite fit into the typical model of the pathway activation). A similar expression analysis was performed here on BCC samples, and the results collated with expression data for dermoids and fibromas are reviewed in Table II.…”

“…Due to similar expression levels of pathway genes, we have included ovarian dermoids in our more recent investigations of ovarian fibroma (7). The latter are very strongly associated with BCNS and therefore expected to be largely caused by PTCH alterations: the incidence of ovarian fibroma in the syndrome patients is several times greater than in the general female population, and this relative increase is comparable to or greater than that of BCCs, the most common syndrome neoplasia.…”

Non-canonical Hedgehog signaling activation in ovarian borderline tumors and ovarian carcinomas

“…We and others have shown that loss of heterozygosity (LOH) of the PTCH1 gene is a frequent event in various malignant and benign tumors of the ovary (26)(27)(28)(29)(30). Benign tumors, such as dermoids and fibromas, also show methylation of the PTCH1 promoter (31), but this does not seem to be the case for ovarian carcinoma (32).…”

Role of the Genetic Factors, Detoxication Systems and Oxidative Stress in the Pathogenesis of Endometriosis and Infertility (Review)

“…[6]. В за-рубежных исследованиях подтверждены факты нали-чия полиморфизма генов при поликистозе яичников, эндометриозе, миоме матки, раке яичников и шейки матки, преждевременном истощении яичников, при-вычном невынашивании и преэклампсии [7][8][9][10][11][12]. Ряд исследований, посвященных изучению генетического полиморфизма при эндометриозе, не показал достовер-ных изменений.…”

The Patched gene is epigenetically regulated in ovarian dermoids and fibromas, but not in basocellular carcinomas

“…The expression data published previously (7,8) show moderately increased activities of various pathway genes. In particular, expression of GLI1 was not consistently increased in all samples, whereas almost all tumors showed some increase in both SHH and SMO expression (7,8) which might in general be compatible with the low malignant potential of the analyzed tumor types; although details of the expression pattern did not quite fit into the typical model of the pathway activation). A similar expression analysis was performed here on BCC samples, and the results collated with expression data for dermoids and fibromas are reviewed in Table II.…”

“…Due to similar expression levels of pathway genes, we have included ovarian dermoids in our more recent investigations of ovarian fibroma (7). The latter are very strongly associated with BCNS and therefore expected to be largely caused by PTCH alterations: the incidence of ovarian fibroma in the syndrome patients is several times greater than in the general female population, and this relative increase is comparable to or greater than that of BCCs, the most common syndrome neoplasia.…”

Non-canonical Hedgehog signaling activation in ovarian borderline tumors and ovarian carcinomas

“…We and others have shown that loss of heterozygosity (LOH) of the PTCH1 gene is a frequent event in various malignant and benign tumors of the ovary (26)(27)(28)(29)(30). Benign tumors, such as dermoids and fibromas, also show methylation of the PTCH1 promoter (31), but this does not seem to be the case for ovarian carcinoma (32).…”

Role of the Genetic Factors, Detoxication Systems and Oxidative Stress in the Pathogenesis of Endometriosis and Infertility (Review)

“…[6]. В за-рубежных исследованиях подтверждены факты нали-чия полиморфизма генов при поликистозе яичников, эндометриозе, миоме матки, раке яичников и шейки матки, преждевременном истощении яичников, при-вычном невынашивании и преэклампсии [7][8][9][10][11][12]. Ряд исследований, посвященных изучению генетического полиморфизма при эндометриозе, не показал достовер-ных изменений.…”

The Patched gene is epigenetically regulated in ovarian dermoids and fibromas, but not in basocellular carcinomas

“…The expression data published previously (7,8) show moderately increased activities of various pathway genes. In particular, expression of GLI1 was not consistently increased in all samples, whereas almost all tumors showed some increase in both SHH and SMO expression (7,8) which might in general be compatible with the low malignant potential of the analyzed tumor types; although details of the expression pattern did not quite fit into the typical model of the pathway activation). A similar expression analysis was performed here on BCC samples, and the results collated with expression data for dermoids and fibromas are reviewed in Table II.…”

“…Due to similar expression levels of pathway genes, we have included ovarian dermoids in our more recent investigations of ovarian fibroma (7). The latter are very strongly associated with BCNS and therefore expected to be largely caused by PTCH alterations: the incidence of ovarian fibroma in the syndrome patients is several times greater than in the general female population, and this relative increase is comparable to or greater than that of BCCs, the most common syndrome neoplasia.…”

Non-canonical Hedgehog signaling activation in ovarian borderline tumors and ovarian carcinomas

“…We and others have shown that loss of heterozygosity (LOH) of the PTCH1 gene is a frequent event in various malignant and benign tumors of the ovary (26)(27)(28)(29)(30). Benign tumors, such as dermoids and fibromas, also show methylation of the PTCH1 promoter (31), but this does not seem to be the case for ovarian carcinoma (32).…”

Role of the Genetic Factors, Detoxication Systems and Oxidative Stress in the Pathogenesis of Endometriosis and Infertility (Review)

“…[6]. В за-рубежных исследованиях подтверждены факты нали-чия полиморфизма генов при поликистозе яичников, эндометриозе, миоме матки, раке яичников и шейки матки, преждевременном истощении яичников, при-вычном невынашивании и преэклампсии [7][8][9][10][11][12]. Ряд исследований, посвященных изучению генетического полиморфизма при эндометриозе, не показал достовер-ных изменений.…”