CCND1 rearrangements and cyclin D1 overexpression in renal oncocytomas: frequency, clinicopathologic features, and utility in differentiation from chromophobe renal cell carcinoma

Sukov, William R.; Ketterling, Rhett P.; Lager, Donna J.; Carlson, Austin W.; Sinnwell, Jason P.; Chow, George K.; Jenkins, Robert B.; Cheville, John C.

doi:10.1016/j.humpath.2009.01.016

Cited by 40 publications

(28 citation statements)

References 23 publications

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“…Translocations between 11q13 and other chromosomal regions (e.g. t(5;11)(q35;q13); t(6;11)(p21;q13); t(7;11)(q11.2;q13)) appear to define a subset of renal oncocytomas [11,12,20,24] and suggest that activation of genes mapping to 11q13 is potentially responsible for the oncogenic properties of these translocations. Among the genes mapping to 11q13 is the Cyclin D1 gene (CCND1) that could be the target of these rearrangements.…”

Section: Discussionmentioning

confidence: 99%

“…These include genetic changes of the nuclear [12,18,20,21,24] and mitochondrial [8,14,[16][17][18][19] DNA. Particularly relevant are genetic alterations that cause disassembly of Complex I of the mitochondrial respiratory chain [8,13,14,56,58].…”

Section: Discussionmentioning

confidence: 99%

“…poor response to radioactive iodide treatment in thyroid oncocytic tumours), as well as different molecular profiles [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

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Genomic profiling of mitochondrion-rich breast carcinoma: chromosomal changes may be relevant for mitochondria accumulation and tumour biology

Geyer¹,

Biase

Lambros³

et al. 2011

Breast Cancer Res Treat

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Oncocytic carcinomas are composed of mitochondrion-rich cells. Though recognised by the WHO classification as a histological special type of breast cancer, their status as a discrete pathological entity remains a matter of contention. Given that oncocytic tumours of other anatomical sites display distinct clinico-pathological and molecular features, we sought to define the molecular genetic features of mitochondrion-rich breast tumours and to compare them with a series of histological grade- and oestrogen receptor status-matched invasive ductal carcinomas of no special type. Seventeen mitochondrion-rich breast carcinomas, including nine bona fide oncocytic carcinomas, were profiled with antibodies against oestrogen, progesterone and androgen receptors, HER2, Ki67, GCDFP-15, chromogranin, epithelial membrane antigen, cytokeratin 7, cytokeratin 14, CD68 and mitochondria antigen. These tumours were microdissected and DNA extracted from samples with >70% of tumour cells. Fourteen cases yielded DNA of sufficient quality/quantity and were subjected to high-resolution microarray comparative genomic hybridisation analysis. The genomic profiles were compared to those of 28 grade- and oestrogen receptor status-matched invasive ductal carcinomas of no special type. Oncocytic and other mitochondrion-rich tumours did not differ significantly between themselves. As a group, mitochondrion-rich carcinomas were immunophenotypically heterogenous. Recurrent copy number changes were similar to those described in unselected breast cancers. However, unsupervised and supervised analysis identified a subset of mitochondrion-rich cancers, which often displayed gains of 11q13.1-q13.2 and 19p13. Changes in the latter two chromosomal regions have been shown to be associated with oncocytic tumours of the kidney and thyroid, respectively, and host several nuclear genes with specific mitochondrial function. Our results indicate that in a way akin to oncocytic tumours of other anatomical sites, at least a subset of mitochondrion-rich breast carcinomas may be underpinned by a distinct pattern of chromosomal changes potentially relevant for mitochondria accumulation and constitute a discrete molecular entity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Genomic profiling of mitochondrion-rich breast carcinoma: chromosomal changes may be relevant for mitochondria accumulation and tumour biology

Geyer¹,

Biase

Lambros³

et al. 2011

Breast Cancer Res Treat

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“…The same results were found in renal cell carcinoma. Amplification and polymorphism of CyclinD1 gene may be involved in tumor's proliferation, invasion, grade and stage which can be used as marker for differentiation in renal cell carcinoma [21][22][23][24][25][26] . These outcomes showed that over-expression of CyclinD1 was closely related to proliferation and invasion of tumor and could be looked as an indicator to determine prognosis of renal cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of proliferation induced by cyclin D1 gene silence in human renal carcinoma ACHN cells

Wang

Guo

Chen

et al. 2010

Chin. J. Cancer Res.

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Objective:To confirm feasibility of Cyclin D1 gene as a new target for cancer gene therapy and to verify the effectiveness of shRNA expression vector-mediated gene silencing.Methods: A RNA interference DNA template targeting Cyclin D1 gene was designed and synthesized. By ligation, the fragment was inserted into Pgenesil-1-U6 to constract the recombinant plasmid Pgenesil-shRNA-Cyclin D1. The identified recombinant plasmid was transfected into ACHN cells with lipofactamine. Cyclin D1 mRNA and protein expression was analyzed by RT-PCR and western-blotting. MTT method was used for observing cell proliferation and drawing growth curve. The cell cycle and ratios of apoptotic cell were assessed by flow cytometric detection. The ability of invasion of cell migration was detected by Transwell chamber invasive models.Results: The plasmid was constructed successfully. After interference, The expression rate of Cyclin D1 mRNA decreased to 0.10±0.04 in Cyclin D1-shRNA(experimental) group and were significantly lower than Pgenesil-NC (negative) group (0.92±0.03) and ACHN (blank control) group(0.94±0.04)(P<0.05). As well, the expression rate of Cyclin D1 protein was decreased evidently in experimental group. The results of flow cytometric detection showed that, including early and late apoptotic cells, the apoptotic ratio of experimental group increased to (37.26±0.60)% significantly, while, the negative group and blank control group were only (4.62±0.40)% and (5.95±1.20)%, respectively. The cell growth curves indicated that the proliferation of experimental group cells was inhibited significantly(P<0.05) and Transwell results suggested that the abilities of invasion cells transfected with Pgenesil-CyclinD1-shRNA decreased conspicuously(P<0.05).Conclusion: The shRNA can inhibit Cyclin D1 expression, specifically and persistently. The down-regulation of Cyclin D1 expression can inhibit the proliferation and induce the apoptosis of renal cell adenocarcinoma cell line ACHN.

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“…Once candidate TUMAPs were identified, immunogenicity was assessed using peripheral blood mononuclear cells (PBMCs) derived from healthy donors. A final set of 9 TUMAPs was derived, representing the following antigens: PLIN2 and APOL1, expressed on the surface of lipid droplets and associated with RCC 15 CCND1, a key cell cycle mediator with documented aberrations in RCC 16 GUCY1A3, involved in cGMP synthesis and angiogenesis 17,18 PRUNE2, overexpressed in genitourinary cancers 19 MET, a transmembrane receptor that binds hepatocyte growth factor (HGF), with a well documented role in RCC pathogenesis 20-22 RGS5, a cell cycle regulator 23 MUC1, a cell surface glycoprotein that can mask surrounding antigenic cell surface proteins 24 MMP7, involved in regulation of the extracellular matrix 25 IMA901 was first assessed in a phase I study including a total of 28 patients, including 15 treatment-naïve patients and 13 patients with heavily refractory disease. 14 The latter cohort had received up to 3 prior lines of therapy, primarily comprised of cytokines with or without cytotoxic agents.…”

Section: Multipeptide Vaccines: Ima901mentioning

confidence: 99%

A New Age for Vaccine Therapy in Renal Cell Carcinoma

Pal

Hu²,

Figlin³

2013

The Cancer Journal

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Over the past several years, the dominant paradigm in drug development for metastatic renal cell carcinoma (mRCC) has been to more selectively and potently target moieties such as the vascular endothelial growth factor receptor (VEGFR). The effectiveness of this strategy appears to be nearing a plateau, however, underscoring the need for novel approaches. Vaccine-based therapies represent one such approach. Several distinct vaccines are currently being examined in mRCC, each utilizing a distinct mechanism of action. For instance, the autologous dendritic cell vaccine AGS-003 utilizes patient-specific antigens derived from primary tumor tissue. In contrast, the poxvirus vaccine TG4010 produces an antigenic response to MUC1, a cell surface glycoprotein that reduces cell-cell interactions and thereby precludes contact inhibition. Other vaccines elicit a response to a broader spectrum of antigens – for instance, the vaccine IMA901 is based on 9 tumor-associated peptides identified from a novel biotechnology platform combining mass spectroscopy, microarray analysis of RNA expression, and immunogenicity assays. Herein, the current status of vaccine-based therapies for mRCC is described in detail. Furthermore, challenges to clinical implementation (e.g., cost, optimal pairing with targeted agents, appropriate sequencing) are presented.

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CCND1 rearrangements and cyclin D1 overexpression in renal oncocytomas: frequency, clinicopathologic features, and utility in differentiation from chromophobe renal cell carcinoma

Cited by 40 publications

References 23 publications

Genomic profiling of mitochondrion-rich breast carcinoma: chromosomal changes may be relevant for mitochondria accumulation and tumour biology

Genomic profiling of mitochondrion-rich breast carcinoma: chromosomal changes may be relevant for mitochondria accumulation and tumour biology

Inhibition of proliferation induced by cyclin D1 gene silence in human renal carcinoma ACHN cells

A New Age for Vaccine Therapy in Renal Cell Carcinoma

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