A one centimorgan deletion unit on chromosome Xq12 is commonly lost in borderline and invasive epithelial ovarian tumors

Edelson, Mitchell I.; Lau, Ching C.; Colitti, Cristiano V.; Welch, William R.; Bell, Deborah F.; Rs, Berkowitz; Mok, Samuel C.

doi:10.1038/sj.onc.1201479

Cited by 38 publications

(19 citation statements)

References 13 publications

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“…Perinchery et al 24 studied the frequency of losses of chromosome Y in prostate cancer and found that loss of the genes analyzed was more frequent in tumors of advanced stage and grade. An additional study of epithelial ovarian tumors showed a high frequency of LOH at the androgen 31 Our finding that PETs tend to show loss of the whole X chromosome suggests that there is no particular selection for a specific region in this tumor type, a finding also supported by the CGH study of Stumpf et al 13 Overall, our study suggests that loss of sex chromosomes in pancreatic endocrine tumors may be associated with features of malignancy and a poorer prognosis. The possibility that these losses could result from a more generalized chromosomal instability or be an effect of aging is not supported by our results.…”

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confidence: 70%

Sex chromosome anomalies in pancreatic endocrine tumors

Missiaglia

Moore

Williamson

et al. 2002

Intl Journal of Cancer

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We have investigated the status of sex chromosomes in 40 pancreatic endocrine tumors (PETs) using 2 complementary techniques: microsatellite and interphase FISH analysis. Twenty-five tumors were from female and 15 from male patients and included 31 nonfunctioning and 9 functioning PET (6 insulinomas, 2 glucagonomas and 1 VIPoma). Microsatellite and FISH analysis showed concordant results in all cases. PETs from females showed frequent loss of chromosome X (40%) whereas PETs from males showed relatively frequent loss of chromosome Y (36%) but never loss of the X chromosome. Statistical analysis showed significant association of sex chromosome loss with metastases (Spearman correlation test, r ‫؍‬ 0.5, p < 0.001), local invasion (r ‫؍‬ 0.33, p < 0.05) and high proliferation rate measured as Ki-67 index with a 5% cut-off (r ‫؍‬ 0.42, p < 0.02). The analysis also showed that local invasion and metastases were highly correlated (r ‫؍‬ 0.86). Multivariate survival analysis was therefore carried out including local invasion and loss of sex chromosomes. The presence of local invasion increased the risk of death almost 9 times whereas sex chromosome loss was an independent variable associated with a shorter survival period and an increased risk of death of approximately 4-fold.

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supporting

confidence: 70%

Sex chromosome anomalies in pancreatic endocrine tumors

Missiaglia

Moore

Williamson

et al. 2002

Intl Journal of Cancer

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“…Of interest, a 75% rate of loss of heterozygosity at 11q23.3-24.3 that harbors the PR gene locus (44,45) had been reported, and one of us (S.C.M.) recently detected a 40% loss of heterozygosity at Xq11.2-q12 that harbors the AR gene (46). In the present study, we observed significant downregulation of PR and AR mRNA expression in several established ovarian cancer cell lines and in the small number of primary cell cultures established from patients with late serous adenocarcinoma.…”

Section: Fig 2 Sequence Analyses Of the Wild-type Er␣ Transcript (Ementioning

confidence: 99%

Expression of human estrogen receptor-α and -β, progesterone receptor, and androgen receptor mRNA in normal and malignant ovarian epithelial cells

Lau

Mok

1999

Proc. Natl. Acad. Sci. U.S.A.

256

161

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Our understanding of the roles played by sex hormones in ovarian carcinogenesis has been limited by a lack of data concerning the mode of sex hormone action in human ovarian surface epithelial (HOSE) cells, the tissue of origin of >90% of ovarian cancers. We have compared the relative abundance of estrogen receptor (ER)␣, ER␤, progesterone receptor (PR), and androgen receptor (AR) mRNA in four primary cultures of HOSE cells obtained from postmenopausal women to those found in late serous adenocarcinoma primary cell cultures and established ovarian cancer cell lines. We observed coexpression of ER␣ and ER␤ mRNA along with AR and PR transcripts in normal HOSE cells and disruption of ER␣ mRNA expression as well as dramatic down-regulation of PR and AR transcript expression in most ovarian cancer cells. In contrast, levels of ER␤ mRNA were unaffected by the malignant state. Additionally, a novel mutation involving a 32-bp deletion in exon 1 of ER␣ transcripts was detected in the SKOV3 cell line. This mutation would explain why SKOV3 was reported to be ER-positive but estrogen-insensitive. Taken together, these findings suggest that estrogens, signaling via either or both ER subtypes, may play an indispensable role in regulating normal HOSE cell functions. Therefore, loss of ER␣, PR, and AR mRNA expression in HOSE cells may be responsible for neoplastic transformation in this cell type. In contrast, the roles played by ER␤ in normal and malignant HOSE cells remain elusive. Finally, the coexistence of mutated ER␣ mRNA and normal ER␤ transcripts in SKOV3 argues in favor of a dependency of ER␤ action on functional ER␣s.

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“…Reduced DLC-3 mRNA levels could also result from genomic DNA losses. Loss of heterozygosity studies have suggested the presence of one or more tumor suppressor genes on the X chromosome (reviewed in Spatz et al, 2004), and the DLC-3 locus is close to an Xq region commonly lost in ovarian epithelial tumors (Edelson et al, 1998). Generation of DLC-3-specific antibodies will be needed to determine whether DLC-3 expression in tumors is reduced at the protein level and whether this is correlated with changes in mRNA levels.…”

Section: -----------------------------------------------------------Dmentioning

confidence: 99%

Deleted in liver cancer 3 (DLC-3), a novel Rho GTPase-activating protein, is downregulated in cancer and inhibits tumor cell growth

et al. 2007

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A one centimorgan deletion unit on chromosome Xq12 is commonly lost in borderline and invasive epithelial ovarian tumors

Cited by 38 publications

References 13 publications

Sex chromosome anomalies in pancreatic endocrine tumors

Sex chromosome anomalies in pancreatic endocrine tumors

Expression of human estrogen receptor-α and -β, progesterone receptor, and androgen receptor mRNA in normal and malignant ovarian epithelial cells

Deleted in liver cancer 3 (DLC-3), a novel Rho GTPase-activating protein, is downregulated in cancer and inhibits tumor cell growth

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