Comparative study of primary and recurrent ovarian serous carcinomas: comparative genomic hybridization analysis with a potential application for prognosis

Hu, Jie; Khanna, Vineesh; Jones, Matthew W.; Surti, Urvashi

doi:10.1016/s0090-8258(03)00056-8

Cited by 29 publications

(21 citation statements)

References 16 publications

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“…This frequency is high compared with most other CGH studies of ovarian cancers that have reported an average of 10 to 20 breakpoints (copy number changes of 5-10 per tumor), with the most complex case reported showing at most 62 breakpoints (arising from 31 copy number alterations; ref. 23). In our data set, individual tumors showed great variation in the number of changes (compare Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

High-Resolution Single Nucleotide Polymorphism Array Analysis of Epithelial Ovarian Cancer Reveals Numerous Microdeletions and Amplifications

Gorringe

Jacobs²,

Thompson³

et al. 2007

Clinical Cancer Research

156

118

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Purpose: Genetic changes in sporadic ovarian cancer are relatively poorly characterized compared with other tumor types.We have evaluated the use of high-resolution whole genome arrays for the genetic profiling of epithelial ovarian cancer. Experimental Design: We have evaluated 31 primary ovarian cancers and matched normal DNA for loss of heterozygosity and copy number alterations using 500K single nucleotide polymorphism arrays. Results: In addition to identifying the expected large-scale genomic copy number changes, >380 small regions of copy number gain or loss (<500 kb) were identified among the 31 tumors, including 33 regions of high-level gain (>5 copies) and 27 homozygous deletions. The existence of such a high frequency of small regions exhibiting copy number alterations had not been previously suspected because earlier genomic array platforms lacked comparable resolution. Interestingly, many of these regions harbor known cancer genes. For example, one tumor harbored a 350-kb high-level amplification centered on FGFR1 and three tumors showed regions of homozygous loss 109 to 216 kb in size involving the RB1 tumor suppressor gene only. Conclusions: These data suggest that novel cancer genes may be located within the other identified small regions of copy number alteration. Analysis of the number of copy number breakpoints and the distribution of the small regions of copy number change indicate high levels of structural chromosomal genetic instability in ovarian cancer.

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Section: Resultsmentioning

confidence: 99%

High-Resolution Single Nucleotide Polymorphism Array Analysis of Epithelial Ovarian Cancer Reveals Numerous Microdeletions and Amplifications

Gorringe

Jacobs²,

Thompson³

et al. 2007

Clinical Cancer Research

156

118

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show abstract

“…and mean fold changes as determined by microarray and RT-PCR are shown in the top corner of each panel Whole genome expression profiling of ovarian cancer H Donninger et al and 8q24.1-q24.2, respectively, all chromosomal locations reported to be amplified in ovarian cancer (Iwabuchi et al, 1995;Bayani et al, 2002;Hauptmann et al, 2002;Hu et al, 2003;Israeli et al, 2003). Similarly, MGC8721, ANAPC4, RECK and SLIT2 located at 8p12, 4p15.31, 9p13-p12 and 4p15.2, respectively, are examples of downregulated genes that occur at chromosomal locations previously reported to be frequently lost in ovarian carcinomas (Iwabuchi et al, 1995;Bayani et al, 2002;Hauptmann et al, 2002;Hu et al, 2003;Israeli et al, 2003). Determining the precise mechanism of dysregulation of these genes will require CGH and LOH analysis on the same samples subjected to expression profiling.…”

Section: Discussionmentioning

confidence: 99%

Whole genome expression profiling of advance stage papillary serous ovarian cancer reveals activated pathways

et al. 2004

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“…In sporadic cancers of the ovary, the rearrangements most frequently found are located in regions 1q, 2p, 2q, 3q, 6q, 7q, 8q, 12p, 17q, 18q, 20q, ch X for gains and in ch4, 6q, 8p, 13q, 16q, 18q, Xq for losses (48). It has even been shown that these profiles are distinctly different between sporadic ovarian cancers and ovarian cancers of a hereditary type due to BRCA mutation (49)(50)(51): genomic imbalances appear to be more numerous in case of genetic risk, probably because there is less DNA repair (one of the functions of BRCA) and the genome is thus more fragile.…”

Section: Ovarian Dysplasiamentioning

confidence: 99%

“…So in hereditary ovarian cancers related with BRCA mutations, very frequent chromosome amplifications at 1q, 2q, 3q, and 8q along with deletions at 9q and a chromosome 19 were often found (49)(50)(51). CGH thus allows specific molecular profiles to be established.…”

Section: Ovarian Dysplasiamentioning

confidence: 99%

“…It has even been shown that these profiles are distinctly different between sporadic ovarian cancers and ovarian cancers of a hereditary type due to BRCA mutation (49)(50)(51). And yet these secondary rearrangements-probably responsible for continued proliferation and the metastatic risk-do not necessarily have any direct link with the pathogenesis and tumorigenesis.…”

Section: Ovarian Dysplasiamentioning

confidence: 99%

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Early Telomere Shortening and Genomic Instability in Tubo-Ovarian Preneoplastic Lesions

Chêne

Tchirkov

Pierre-Eymard

et al. 2013

Clinical Cancer Research

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Purpose: Genetic instability plays an important role in ovarian carcinogenesis. We investigated the level of telomere shortening and genomic instability in early and preinvasive stages of ovarian cancer, serous tubal intraepithelial carcinoma (STIC), and tubo-ovarian dysplasia (TOD).Experimental Design: Fifty-one TOD from prophylactic salpingo-oophorectomies with BRCA1 or 2 mutation, 12 STICs, 53 tubo-ovarian high-grade serous carcinoma, and 36 noncancerous controls were laser capture microdissected from formalin-fixed, paraffin-embedded sections, analyzed by comparative genomic hybridization (array CGH) and for telomere length (using quantitative real-time PCR based on the Cawthon's method). TOD and STICs were defined by morphologic scores and immunohistochemical expressions of p53, Ki67, and gH2AX.Results: TOD showed marked telomere shortening compared with noncancerous controls (P < 10 À7 ).STICs had even shorter telomeres than TOD (P ¼ 0.0008). Ovarian carcinoma had shorter telomeres than controls but longer than STICs and dysplasia. In TOD, telomeres were significantly shorter in those with BRCA1 mutation than in those with BRCA2 mutation (P ¼ 0.005). In addition, gH2AX expression in TOD and STIC groups with short telomeres was significantly increased (P < 10 À7 ). In dysplastic epithelium, we found subtle genomic alterations, in contrast to more important genomic imbalances in STICs. The total number of genetic alterations was the highest in ovarian cancers. Conclusions: These findings suggest that genetic instability occurs in early stages of ovarian tumorigenesis. STICs and noninvasive dysplasia are likely an important step in early serous ovarian neoplasia.

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Comparative study of primary and recurrent ovarian serous carcinomas: comparative genomic hybridization analysis with a potential application for prognosis

Cited by 29 publications

References 16 publications

High-Resolution Single Nucleotide Polymorphism Array Analysis of Epithelial Ovarian Cancer Reveals Numerous Microdeletions and Amplifications

High-Resolution Single Nucleotide Polymorphism Array Analysis of Epithelial Ovarian Cancer Reveals Numerous Microdeletions and Amplifications

Whole genome expression profiling of advance stage papillary serous ovarian cancer reveals activated pathways

Early Telomere Shortening and Genomic Instability in Tubo-Ovarian Preneoplastic Lesions

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