Monosomy 22 in a mixed germ cell-sex cord-stromal tumor of the ovary

Speleman, Frank; Dermaut, Bart; Potter, CW; Gele, Mireille Van; Roy, Nadine Van; Paepe, A De; Laureys, Geneviève

doi:10.1016/s0165-4608(97)90313-7

Cited by 2 publications

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“…A number of previous studies noted trisomy 12 to be a frequent abnormality in tumors of the female genitourinary tract. It is a relatively common finding in sex cord-stromal tumors (11,28,29,(37)(38)(39)(40). In agreement with these studies, we detected trisomy 12 by FISH analysis in five GCT (25%).…”

Section: Discussionsupporting

confidence: 90%

“…Recent examinations of archival material by FISH have failed to confirm the high prevalence of trisomy 12 initially thought to be present in GCT and other sex cord-stromal tumors (8 -10). Several other aberrations including monosomy 22, trisomy 14, and rearrangement of 6q have been reported (11). To the best of our knowledge, studies using comparative genomic hybridization (CGH) have not been reported so far for GCT.…”

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confidence: 99%

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Characteristic Pattern of Genetic Aberrations in Ovarian Granulosa Cell Tumors

Mayr¹,

Kaltz-Wittmer²,

Arbogast³

et al. 2002

Mod Pathol

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The cytogenetic abnormalities of granulosa cell tumors (GCT) of the ovary are only partially known. Up to now, mainly numerical chromosomal aberrations have been described. Therefore we performed a comprehensive study on paraffin-embedded material of 20 GCT (17 adult, 3 juvenile; patient age between 16 and 78 y) combining comparative genomic hybridization (CGH); fluorescence in situ hybridization (FISH) using DNA-specific probes for chromosome 12, 17, 22, and X; DNA cytometry; and immunohistochemistry (inhibin, p53, Ki67).By DNA cytometry, 16 of 20 tumors (80%) were diploid. However, 6 of 16 diploid tumors (37%) showed aberrations by FISH. FISH revealed monosomy 22 in 8/18 cases (40%); trisomy 12 in 5/20 (25%); monosomy X in 2/20 (10%); and loss of chromosome 17 in one case (5%). The main findings by CGH were gains of chromosomes 12 (6 cases, 33%) and 14 (6 cases, 33%) and losses of chromosomes 22 (7 cases, 35%) and X (1 case, 5%), mostly comprising whole chromosomes or chromosome arms. Inhibin and p53 were expressed in 100% and 95% of the tumors, respectively. The Ki67 index ranged from 0% to 61%. Neither immunohistochemistry, nor DNA cytometry and molecular genetic analysis, provided statistically significant prognostic information.In summary, our study reveals a distinctive pattern of cytogenetic alterations in GCT. Our observations confirm earlier reports that trisomy 12 and 14 are frequent aberrations; however, monosomy 22 seemingly is even more prevalent. Granulosa cell tumors of the ovary (GCT) are much less common than epithelial ovarian cancer. These tumors account for 1.5% of all ovarian neoplasms and for 6% of malignant ovarian tumors. Sixty-five percent of patients are postmenopausal; Ͻ5% are prepubertal. The juvenile granulosa cell tumor is a distinctive form of GCT that occurs almost exclusively in children and young adults. More than 95% of the GCT are unilateral and confined to the ovary.

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Section: Discussionsupporting

confidence: 90%

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confidence: 99%

Characteristic Pattern of Genetic Aberrations in Ovarian Granulosa Cell Tumors

Mayr¹,

Kaltz-Wittmer²,

Arbogast³

et al. 2002

Mod Pathol

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“…The loss of fidelity in the inherent order of replication of allelic pairs during cell division provides a source for generating mutations involving genetic (aneuploidy) and epigenetic (gene silencing or allelic inactivation) events required for the generation and establishment of malignant phenotype (Duesberg et al, 2000). As reported in previous studies and in the present findings, monosomy of chromosome 22 and trisomy 14 provide a prognostic factor for the disease (Speleman et al, 1997). This emphasizes the association between MGMT, CDH1, SYK and RARb methylation and aneuploidy.…”

Section: Discussionsupporting

confidence: 78%

“…In light of the data, the present finding of monosomy 22 as the sole chromosome change in these tumours suggests that this karyotypic change, possibly followed by the acquisition of an extra chromosome 14 (trisomy), may be nonrandom but an early, nonobligatory event of the tumorigenesis of GCTs of the ovary (Dal Cin et al, 1997;Speleman et al, 1997, Van den Berghe et al, 1999. The loss of fidelity in the inherent order of replication of allelic pairs during cell division provides a source for generating mutations involving genetic (aneuploidy) and epigenetic (gene silencing or allelic inactivation) events required for the generation and establishment of malignant phenotype (Duesberg et al, 2000).…”

Section: Discussionmentioning

confidence: 78%

Promoter hypermethylation of MGMT, CDH1, RAR-β and SYK tumour suppressor genes in granulosa cell tumours (GCTs) of ovarian origin

et al. 2004

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Ovarian carcinoma (OC) is a leading cause of death among women throughout the world. A number of cancer-associated genes have been shown to be inactivated by hypermethylation of CpG islands during tumorigenesis. We tested the hypothesis that methylation status of MGMT, CDH1, RAR-b and SYK could be important in the ovarian tumorigenic process and can lead to the gene(s) inactivation. Therefore, we assessed the promoter hypermethylation of MGMT, CDH1, RAR-b and SYK in 43 ovarian granulosa cell tumours (GCTs) (adult type) using methylation-specific PCR. These tumours are relatively rare, accounting for approximately 3% of all ovarian cancers. Hypermethylation of MGMT (in 14 tumours), CDH1 (in nine tumours), RAR-b (in eight tumours) and SYK (in seven tumours) have been found. Selective loss of RAR-b and RAR-b2 mRNA has been found in seven patients, while that of MGMT and SYK in three patients who also show aberrant methylation in promoter region of RAR-b in addition to MGMT, SYK and CDH1 genes. Promoter CpG hypermethylation may be an alternative to mutation(s) to inactivate tumour suppressor genes such as MGMT, CDH1, RAR-b and SYK, and this can also be an early event in the pathogenesis of OCs. Moreover, hypermethylation of the MGMT and CDH1, MGMT and RAR-b and CDH1 and RAR-b promoters occurred concordantly (Po 0.001, 0.0421 and 0.0005 respectively; Fischer's exact test). In addition to this, monosomy 22 and trisomy 14 have also been found in 10 tumours. It is clear from the results that hypermethylation of the promoter region of these tumour suppressor genes, monosomy 22 and trisomy 14, may be critical steps in the tumorigenesis, which consequently play a permissive role for tumour aggressiveness. All these events might play an important role in the early clinical diagnosis of the disease. Our results, therefore, suggest a potential role for epigenetic modification of these critical tumour suppressor genes in pathways relevant to the transformation and differentiation of rare type of ovarian cancer (GCTs).

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Monosomy 22 in a mixed germ cell-sex cord-stromal tumor of the ovary

Cited by 2 publications

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Characteristic Pattern of Genetic Aberrations in Ovarian Granulosa Cell Tumors

Characteristic Pattern of Genetic Aberrations in Ovarian Granulosa Cell Tumors

Promoter hypermethylation of MGMT, CDH1, RAR-β and SYK tumour suppressor genes in granulosa cell tumours (GCTs) of ovarian origin

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