RNF43 mutations are recurrent in Chinese patients with mucinous ovarian carcinoma but absent in other subtypes of ovarian cancer

Zou, Yang; Wang, Feng; Liu, Faying; Huang, Meizhen; Li, Wei; Yuan, Xiao-Qun; Huang, Ouping; He, Ming

doi:10.1016/j.gene.2013.08.054

Cited by 26 publications

(28 citation statements)

References 22 publications

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“…The available clinical data of these patients are as described previously (25,26). In the present study, a total of 251 Chinese samples with distinct subtypes of ovarian carcinoma were screened for the presence of potential hotspot mutations in the DICER1, CTCF, RPL22, DNMT3A, TRRAP, IDH1 and IDH2 genes.…”

Section: Resultsmentioning

confidence: 99%

“…Only those patients with >70% of neoplastic cells were recruited in the study. The sample cohort contained 76 ovarian serous carcinoma, 43 ovarian clear cell carcinoma, 37 ovarian endometrioid carcinoma, 33 ovarian germ cell tumor, 15 mucinous ovarian carcinoma, 18 ovarian sex cord-stromal tumor, 12 other rare subtypes and 17 Krukenberg tumor, and the available clinical data was as described previously (25,26) and in Table I. Informed consent conforming to the tenets of the Declaration of Helsinki was obtained from each patient prior to the study.…”

Section: Methodsmentioning

confidence: 99%

“…The Omega FFPE DNA kit (Omega Bio-tek Inc., Doraville, GA, USA) was used to isolate the DNA from the FFPE tissues. The polymerase chain reaction (PCR) primers were as summarized previously (25,27) and are shown in Table II. PCR reactions were performed in a total volume of 25 µl, containing 50 ng genomic DNA, 2 units of LA Taq DNA Polymerase (Takara Biotechnology Dalian Co. Ltd., Liaoning, China), 300 µM of each dNTP and 0.2 µM of each primer.…”

Section: Methodsmentioning

confidence: 99%

“…PCR reactions were performed in a total volume of 25 µl, containing 50 ng genomic DNA, 2 units of LA Taq DNA Polymerase (Takara Biotechnology Dalian Co. Ltd., Liaoning, China), 300 µM of each dNTP and 0.2 µM of each primer. The amplification reaction was performed in a Thermal Cycler 2720 (Applied Biosystems, Foster City, CA, USA) and employed one denaturation cycle of 94˚C for 3 min, 35 amplification cycles of 94˚C for 30 sec, 50-60˚C (Table II) As per references (25,26); POLE1, polymerase (DNA directed) ε, catalytic subunit; RNF43, ring finger protein 43.…”

Section: Methodsmentioning

confidence: 99%

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Absence of DICER1, CTCF, RPL22, DNMT3A, TRRAP, IDH1 and IDH2 hotspot mutations in patients with various subtypes of ovarian carcinomas

et al. 2014

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Abstract.Cancer is caused by multiple genetic alterations within cells. Recently, large-scale sequencing has identified frequent ribonuclease type III (DICER1), CCCTC-binding factor (CTCF), ribosomal protein L22 (RPL22), DNA (cytosine-5-)-methyltransferase 3α (DNMT3A), transformation/transcription domain-associated protein (TRRAP), isocitrate dehydrogenase (IDH)1 and IDH2 hotspot mutations in diverse types of cancer. However, it remains largely unknown whether these mutations also exist in ovarian carcinomas. In the present study, a collection of 251 patients with distinct subtypes of ovarian carcinomas were recruited and sequenced for the presence of these hotspot mutations. However, no mutations in the seven genes were detected in the samples. These negative results, together with certain recent reports, indicate that the hotspot mutations in the CTCF, RPL22, DNMT3A, TRRAP, IDH1 and IDH2 genes may not be actively involved in the carcinogenesis of ovarian carcinoma. Of note, the DICER1 mutation frequency in Sertoli-Leydig cell tumor in the present study was significantly lower compared to prior observation, and therefore, it is speculated that this discrepancy may be mainly due to the small sample size analyzed in the study. In addition, among these samples, frequent polymerase (DNA directed) ε, catalytic subunit (POLE1) and ring finger protein 43 (RNF43) mutations were identified in endometrioid and mucinous ovarian carcinomas, respectively; thus DICER1, CTCF, RPL22, DNMT3A, TRRAP, IDH1 and IDH2 hotspot mutations may not play synergistic roles with POLE1 or RNF43 mutations in the carcinogenesis of endometrioid or mucinous ovarian carcinomas. IntroductionThe current understanding of human malignancy is that it mainly arises due to the accumulation of multiple genetic alterations, transforming normal cells into malignant cells (1,2). Of these genetic alterations, a myriad of genomic mutation data derived from a high-throughput DNA sequencing technique provided a unique opportunity to profile the mutation spectra underlying human cancers and a large number of significant functional mutations in multiple genes were identified in diverse types of cancer (1,3,4). These genes can be defined as oncogenes or tumor suppressor genes and are being used as molecular markers for diagnosis, staging and prognosis of human cancers (5,6).Ovarian carcinoma constitutes a heterogeneous group of malignancies with significantly different clinical expression, pathological characteristics and genetic etiology (7,8). However, the majority of ovarian carcinomas shared certain common genetic alterations, such as frequent tumor protein p53 (TP53) and PIK3CA, catalytic subunit α mutations (9,10), and patients also exhibited subtype-specific mutations (11-13), which are possibly essential for the differential clinical expression and molecular-targeted therapy in ovarian carcinomas (14,15). These observations emphasized the requirement to identify novel subtype-specific molecular genetic aberrations in ovarian carcinomas.Recently, large-scal...

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Absence of DICER1, CTCF, RPL22, DNMT3A, TRRAP, IDH1 and IDH2 hotspot mutations in patients with various subtypes of ovarian carcinomas

et al. 2014

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“…Consistently, simultaneous deletion of these two Wnt modulators in the intestinal epithelium induces formation of unusual adenomas consisting entirely of Lgr5 stem cells and their niche . Indeed, mutations in Rnf43 are seen in some human colon cancer cell lines ) and a variety of human tumor types affecting the bile duct (Ong et al 2012), pancreas (Furukawa et al 2011;Wu et al 2011;Jiang et al 2013), and ovary (Ryland et al 2013;Zou et al 2013). Of interest, the small molecule Wnt secretion inhibitor LGK974 inhibits proliferation and induces differentiation of RNF43 mutant pancreatic adenocarcinoma cell lines even when tested in xenograft models .…”

Section: E3 Ubiquitin Ligases Implied In Wnt-lgr/r-spondin Signalingmentioning

confidence: 99%

The R-spondin/Lgr5/Rnf43 module: regulator of Wnt signal strength

et al. 2014

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Lgr5 was originally discovered as a common Wnt target gene in adult intestinal crypts and colon cancer. It was subsequently identified as an exquisite marker of multiple Wnt-driven adult stem cell types. Lgr5 and its homologs, Lgr4 and Lgr6, constitute the receptors for R-spondins, potent Wnt signal enhancers and stem cell growth factors. The Lgr5/R-spondin complex acts by neutralizing Rnf43 and Znrf3, two transmembrane E3 ligases that remove Wnt receptors from the stem cell surface. Rnf43/Znrf3 are themselves encoded by Wnt target genes and constitute a negative Wnt feedback loop. Thus, adult stem cells are controlled by an intricate interplay of potent Wnt agonists, antagonists, and anti-antagonists.

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