Chromosome 19 rearrangements in ovarian carcinomas: Zinc finger genes are particularly targeted

Smebye, Marianne L.; Sveen, Anita; Haugom, Lisbeth; Davidson, Ben; Tropé, Claes G.; Heim, Sverre; Skotheim, Rolf Inge; Micci, Francesca

doi:10.1002/gcc.22166

Cited by 5 publications

(4 citation statements)

References 36 publications

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“…Zinc Finger Protein 223 (ZNF223) is a zinc-finger protein of unknown function. ZNF223 upregulation has been associated with a subset of ovarian carcinomas [ 46 ]. Phosphodiesterase 6G (PDE6G) encodes the gamma subunit of cyclic GMP-phosphodiesterase and plays a role in the pathogenesis of retinitis pigmentosa [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Sentinel Lymph Node Gene Expression Signature Predicts Recurrence-Free Survival in Cutaneous Melanoma

Karapetyan

Gooding

et al. 2022

Cancers

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We sought to develop a sentinel lymph node gene expression signature score predictive of disease recurrence in patients with cutaneous melanoma. Gene expression profiling was performed on SLN biopsies using U133A 2.0 Affymetrix gene chips. The top 25 genes associated with recurrence-free survival (RFS) were selected and a penalized regression function was used to select 12 genes with a non-zero coefficient. A proportional hazards regression model was used to evaluate the association between clinical covariates, gene signature score, and RFS. Among the 45 patients evaluated, 23 (51%) had a positive SLN. Twenty-one (46.7%) patients developed disease recurrence. For the top 25 differentially expressed genes (DEG), 12 non-zero penalized coefficients were estimated (CLGN, C1QTNF3, ADORA3, ARHGAP8, DCTN1, ASPSCR1, CHRFAM7A, ZNF223, PDE6G, CXCL3, HEXIM1, HLA-DRB). This 12-gene signature score was significantly associated with RFS (p < 0.0001) and produced a bootstrap C index of 0.888. In univariate analysis, Breslow thickness, presence of primary tumor ulceration, SLN positivity were each significantly associated with RFS. After simultaneously adjusting for these prognostic factors in relation to the gene signature, the 12-gene score remained a significant independent predictor for RFS (p < 0.0001). This SLN 12-gene signature risk score is associated with melanoma recurrence regardless of SLN status and may be used as a prognostic factor for RFS.

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Section: Discussionmentioning

confidence: 99%

Sentinel Lymph Node Gene Expression Signature Predicts Recurrence-Free Survival in Cutaneous Melanoma

Karapetyan

Gooding

et al. 2022

Cancers

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“…Knockdown screens have shown that ZNF100 knockdown sensitizes gastrointestinal stromal tumor cells to sunitinib and imatinib treatment [ 21 ]. The 19p12-13 region is amplified in ovarian cancer and ZNF100, and other ZNF genes, show increased expression in tumors with these amplifications [ 22 ]. In a public dataset, we identified an association between greater ZNF100 expression and shorter OS but we have not been able to find direct evidence that candidate outcome variants at 19p12 up-regulate ZNF100 expression.…”

Section: Discussionmentioning

confidence: 99%

Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci

Glubb¹,

Johnatty²,

Quinn³

et al. 2017

Oncotarget

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We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. Bioinformatic and functional genetic analyses indicated that MEF2D and ZNF100 are targets of candidate outcome variants at 1q22 and 19p12, respectively. At 19p12, the chromatin interaction of a putative regulatory element with the ZNF100 promoter region correlated with candidate outcome variants. At 1q22, putative regulatory elements enhanced MEF2D promoter activity and haplotypes containing candidate outcome variants modulated these effects. In a public dataset, MEF2D and ZNF100 expression were both associated with ovarian cancer progression-free or overall survival time. In an extended set of 6,162 epithelial ovarian cancer patients, we found that functional candidates at the 1q22 and 19p12 loci, as well as other regional variants, were nominally associated with patient outcome; however, no associations reached our threshold for statistical significance (p<1×10-5). Larger patient numbers will be needed to convincingly identify any true associations at these loci.

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“…RNA from each sample was individually amplified, reversely transcribed, fragmented, and labeled. Labeled sense strand cDNA was hybridized onto the arrays for 16–18 h, after which the arrays were washed, stained, and scanned as described earlier [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

Involvement of DPP9 in gene fusions in serous ovarian carcinoma

et al. 2017

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BackgroundA fusion gene is a hybrid gene consisting of parts from two previously independent genes. Chromosomal rearrangements leading to gene breakage are frequent in high-grade serous ovarian carcinomas and have been reported as a common mechanism for inactivating tumor suppressor genes. However, no fusion genes have been repeatedly reported to be recurrent driver events in ovarian carcinogenesis. We combined genomic and transcriptomic information to identify novel fusion gene candidates and aberrantly expressed genes in ovarian carcinomas.MethodsExamined were 19 previously karyotyped ovarian carcinomas (18 of the serous histotype and one undifferentiated). First, karyotypic aberrations were compared to fusion gene candidates identified by RNA sequencing (RNA-seq). In addition, we used exon-level gene expression microarrays as a screening tool to identify aberrantly expressed genes possibly involved in gene fusion events, and compared the findings to the RNA-seq data.ResultsWe found a DPP9-PPP6R3 fusion transcript in one tumor showing a matching genomic 11;19-translocation. Another tumor had a rearrangement of DPP9 with PLIN3. Both rearrangements were associated with diminished expression of the 3′ end of DPP9 corresponding to the breakpoints identified by RNA-seq. For the exon-level expression analysis, candidate fusion partner genes were ranked according to deviating expression compared to the median of the sample set. The results were collated with data obtained from the RNA-seq analysis. Several fusion candidates were identified, among them TMEM123-MMP27, ZBTB46-WFDC13, and PLXNB1-PRKAR2A, all of which led to stronger expression of the 3′ genes. In view of our previous findings of nonrandom rearrangements of chromosome 19 in this cancer type, particular emphasis was given to changes of this chromosome and a DDA1-FAM129C fusion event was identified.ConclusionsWe have identified novel fusion gene candidates in high-grade serous ovarian carcinoma. DPP9 was involved in two different fusion transcripts that both resulted in deregulated expression of the 3′ end of the transcript and thus possible loss of the active domains in the DPP9 protein. The identified rearrangements might play a role in tumorigenesis or tumor progression.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3625-6) contains supplementary material, which is available to authorized users.

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Chromosome 19 rearrangements in ovarian carcinomas: Zinc finger genes are particularly targeted

Cited by 5 publications

References 36 publications

Sentinel Lymph Node Gene Expression Signature Predicts Recurrence-Free Survival in Cutaneous Melanoma

Sentinel Lymph Node Gene Expression Signature Predicts Recurrence-Free Survival in Cutaneous Melanoma

Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci

Involvement of DPP9 in gene fusions in serous ovarian carcinoma

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