Prognostic and therapeutic impact of the chromosome 20q13.2 <i>ZNF217</i> locus amplification in ovarian clear cell carcinoma

Rahman, Mohammed Tanjimur; Nakayama, Kentaro; Rahman, Munmun; Nakayama, Naomi; Ishikawa, Masatoshi; Katagiri, Atsuko; Iida, Kouji; Nakayama, Shinichi; Otsuki, Yoshiro; Shih, Ie Ming; Miyazaki, Kohji

doi:10.1002/cncr.26598

Cited by 58 publications

(63 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Absence of prognostic significance of PIK3CA mutations and PI3K-Akt pathway was confirmed in our study as in the previous studies. 10,27,35 In this study, we demonstrated that loss of PTEN expression was not an independent prognostic factor after multivariate analysis; this finding is similar to that of Ho et al 36 ZNF217 amplification was reported to be a poor prognostic factor in the study by Rahman et al, 32 while in this study, we did not find the prognostic effect of ZNF217 amplification. In brief, FIGO staging was the most important and the only prognostic factor in our study.…”

Section: Discussionsupporting

confidence: 89%

“…29,30 Recently, Krig et al 31 reported that ZNF217 could activate the PI3K-Akt pathway by regulating ErbB3 expression in breast cancer cells. ZNF217 amplification and PIK3CA mutations were almost mutually exclusive in the study by Rahman et al 32 In our study, the correlation between PIK3CA mutations and ZNF217 amplification was not statistically significant (data not shown, P ¼ 0.541). PIK3CA mutations and ZNF217 amplification affected 38 cases, and 6 cases (16%) harbored both PIK3CA mutations and ZNF217 amplification.…”

Section: Discussioncontrasting

confidence: 64%

“…The results were not consistent with Rahman's study. 32 Compared with Rahman's study, we used different FISH probes and different criteria for amplification. If we combined activating PIK3CA mutations, ZNF217 amplification and loss of PTEN expression as indicators of activating Akt pathway, the relationship between ARID1A expression and the activating Akt pathway was more statistically significant (P ¼ 0.007) than the PI3K-Akt pathway (P ¼ 0.048).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations and ZNF217 amplification in ovarian clear cell carcinoma

et al. 2014

View full text Add to dashboard Cite

AT-rich interactive domain 1A (ARID1A) is a subunit of switch/sucrose non-fermentable (SWI/SNF) complex. Recently, alterations of ARID1A gene, phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) pathway and zinc-finger protein 217 (ZNF217) gene have been identified as frequent molecular genetic changes in ovarian clear cell carcinoma. The relationships between these events have not been studied and integrated in the same cohort. This study was aimed at determining the correlation between these molecular events and other clinicopathological factors, including the prognostic impacts of these clinicopathological factors. A total of 68 ovarian clear cell carcinoma cases were collected and subjected to immunohistochemistry testing for ARID1A, SMARCA2, SMARCA4, SMARCB1 and phosphatase and tensin homolog (PTEN), mutation analysis for phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene and fluorescence in situ hybridization for ZNF217 amplification. The correlations between ARID1A expression, PI3K-Akt pathway, ZNF217 amplification and other clinicopathological factors were analyzed. Loss of ARID1A expression was present in 35 cases (52%) and loss of SMARCA2 expression occurred in 1 case. SMARCA4 and SMARCB1 expressions were preserved in all cases. PIK3CA mutations were present in 23 cases (34%) and loss of PTEN expression occurred in 8 cases (12%). Alterations in the PI3K-Akt pathway (PIK3CA mutations or loss of PTEN expression) were found in 42 cases (62%). ZNF217 amplification was detected in 21 cases (31%). Loss of ARID1A expression was significantly related to younger patient age (P ¼ 0.048), PI3K-Akt pathway activation (P ¼ 0.046) and ZNF217 amplification (P ¼ 0.028). All of the clinicopathological factors were not prognostic factors for ovarian clear cell carcinoma after multivariate analysis, except International Federation of Gynecology and Obstetrics staging (P ¼ 0.001). Our results showed that loss of ARID1A expression usually coexisted with PI3K-Akt pathway activation and/or ZNF217 amplification. Synergic effects of loss of ARID1A and PI3K-Akt pathway activation as well as ZNF217 amplification may be related to the development of ovarian clear cell carcinoma.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussioncontrasting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations and ZNF217 amplification in ovarian clear cell carcinoma

et al. 2014

View full text Add to dashboard Cite

show abstract

“…In previous studies, molecular alterations in ovarian clear cell carcinomas, including ARID1A, PIK3CA, and ZNF217, were either not considered a prognostic factor or signified different conclusions. 22,24,[32][33][34][35][36][37] Our study is the first report on the prognostic impact of TERT promoter mutations in early-stage ovarian clear cell carcinomas. TERT promoter mutations may have a role in the development of chemoresistance, but more in-depth investigations are necessary.…”

Section: Discussionmentioning

confidence: 68%

Molecular alterations in endometrial and ovarian clear cell carcinomas: clinical impacts of telomerase reverse transcriptase promoter mutation

et al. 2015

View full text Add to dashboard Cite

Recently, mutations of telomerase reverse transcriptase (TERT) promoter were found in several types of cancer. A few reports demonstrate TERT promoter mutations in ovarian clear cell carcinomas but endometrial clear cell carcinoma has not been studied. The aims of this study were to compare differences of molecular alterations and clinical factors, and identify their prognostic impact in endometrial and ovarian clear cell carcinomas. We evaluated mutations of the TERT promoter and PIK3CA, expression of ARID1A, and other clinicopathological factors in 56 ovarian and 14 endometrial clear cell carcinomas. We found that TERT promoter mutations were present in 21% (3/14) of endometrial clear cell carcinomas and 16% (9/56) of ovarian clear cell carcinomas. Compared with ovarian clear cell carcinomas, endometrial clear cell carcinomas showed older mean patient age (Po0.001), preserved ARID1A immunoreactivity (P ¼ 0.017) and infrequent PIK3CA mutation (P ¼ 0.025). In ovarian clear cell carcinomas, TERT promoter mutations were correlated with patient age 445 (P ¼ 0.045) and preserved ARID1A expression (P ¼ 0.003). In cases of endometrial clear cell carcinoma, TERT promoter mutations were not statistically associated with any other clinicopathological factors. In ovarian clear cell carcinoma patients with early FIGO stage (stages I and II), TERT promoter mutation was an independent prognostic factor and correlated with a shorter disease-free survival and overall survival (P ¼ 0.015 and 0.009, respectively). In recurrent ovarian clear cell carcinoma patients with early FIGO stage, TERT promoter mutations were associated with early relapse within 6 months (P ¼ 0.018). We concluded that TERT promoter mutations were present in endometrial and ovarian clear cell carcinomas. Distinct molecular alteration patterns in endometrial and ovarian clear cell carcinomas implied different processes of tumorigenesis in these morphologically similar tumors. In ovarian clear cell carcinoma of early FIGO stage, patients with TERT promoter mutation require close follow-up during the initial 6 months following chemotherapy. Modern Pathology (2015) 28, 303-311; doi:10.1038/modpathol.2014 published online 1 August 2014 Ovarian clear cell carcinoma represents 5-25% of all epithelial ovarian carcinomas with geographic variation. 1 Compared with high-grade serous adenocarcinomas, ovarian clear cell carcinomas are characterized by a higher incidence among Asians, younger patient age and early tumor staging at presentation, association with endometriosis, higher frequencies of AT-rich interactive domain 1 A (ARID1A) mutation and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation, and higher resistance to first-line platinum and taxane-based chemotherapy.

show abstract

“…For example amplifications in the long arm of chromosome 20 have been associated with poor prognosis and chemotherapy resistance in breast and ovarian carcinoma [61, 62]. In head and neck squamous cell carcinoma 11q13 amplification is a marker of poor prognosis, whereas 3p and 11q loss is associated with resistance to chemotherapy and/or radiotherapy [63, 64].…”

Section: Cytogenetic Alterationsmentioning

confidence: 99%

Genetic and molecular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment

2016

View full text Add to dashboard Cite

Olfactory neuroblastoma (ONB, Esthesioneuroblastoma) is an infrequent neoplasm of the head and neck area derived from olfactory neuroepithelium. Despite relatively good prognosis a subset of patients shows recurrence, progression and/or metastatic disease, which requires additional treatment. However, neither prognostic nor predictive factors are well specified. Thus, we performed a literature search for the currently available data on disturbances in molecular pathways, cytogenetic changes and results gained by next generation sequencing (NGS) approaches in ONB in order to gain an overview of genetic alterations which might be useful for treating patients with ONB. We present briefly ONB molecular pathogenesis and propose potential therapeutic targets and prognostic factors. Possible therapeutic targets in ONB include: receptor tyrosine kinases (c-kit, PDGFR-b, TrkB; EGFR); somatostatin receptor; FGF-FGFR1 signaling; Sonic hedgehog pathway; apoptosis-related pathways (Bcl-2, TRAIL) and neoangiogenesis (VEGF; KDR). Furthermore, we compare high- and low-grade ONB, and describe its frequent mimicker: sinonasal neuroendocrine carcinoma. ONB is often a therapeutic challenge, so our goal should be the implementation of acquired knowledge into clinical practice, especially at pretreated, recurrent and metastatic stages. Moreover, the multicenter molecular studies are needed to increase the amount of available data.

show abstract

Prognostic and therapeutic impact of the chromosome 20q13.2 ZNF217 locus amplification in ovarian clear cell carcinoma

Cited by 58 publications

References 86 publications

Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations and ZNF217 amplification in ovarian clear cell carcinoma

Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations and ZNF217 amplification in ovarian clear cell carcinoma

Molecular alterations in endometrial and ovarian clear cell carcinomas: clinical impacts of telomerase reverse transcriptase promoter mutation

Genetic and molecular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment

Contact Info

Product

Resources

About