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Low DICER1 expression is associated with poor clinical outcome in adrenocortical carcinoma
Low DICER1 expression was associated with poor outcome in several cancers. Recently, hot-spot DICER1 mutations were found in ovarian tumors, and TARBP2 truncating mutations in tumor cell lines with microsatellite instability. In this study, we assessed DICER1 e TRBP protein expression in 154 adult a...
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| Published in: | Oncotarget 2015-09, Vol.6 (26), p.22724-22733 |
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| creator | de Sousa, Gabriela Resende Vieira Ribeiro, Tamaya C Faria, Andre M Mariani, Beatriz M P Lerario, Antonio M Zerbini, Maria Claudia N Soares, Iberê C Wakamatsu, Alda Alves, Venancio A F Mendonca, Berenice B Fragoso, Maria Candida B V Latronico, Ana Claudia Almeida, Madson Q |
| description | Low DICER1 expression was associated with poor outcome in several cancers. Recently, hot-spot DICER1 mutations were found in ovarian tumors, and TARBP2 truncating mutations in tumor cell lines with microsatellite instability. In this study, we assessed DICER1 e TRBP protein expression in 154 adult adrenocortical tumors (75 adenomas and 79 carcinomas). Expression of DICER1 and TARBP2 gene was assessed in a subgroup of 61 tumors. Additionally, we investigated mutations in metal biding sites located at the RNase IIIb domain of DICER1 and in the exon 5 of TARBP2 in 61 tumors. A strong DICER1 expression was demonstrated in 32% of adenomas and in 51% of carcinomas (p = 0.028). Similarly, DICER1 gene overexpression was more frequent in carcinomas (60%) than in adenomas (23%, p = 0.006). But, among adrenocortical carcinomas, a weak DICER1 expression was significantly more frequent in metastatic than in non-metastatic adrenocortical carcinomas (66% vs. 31%; p = 0.002). Additionally, a weak DICER1 expression was significantly correlated with a reduced overall (p = 0.004) and disease-free (p = 0.005) survival. In the multivariate analysis, a weak DICER1 expression (p = 0.048) remained as independent predictor of recurrence. Regarding TARBP2 gene, its protein and gene expression did not correlate with histopathological and clinical parameters. No variant was identified in hot spot areas of DICER1 and TARBP2. In conclusion, a weak DICER1 protein expression was associated with reduced disease-free and overall survival and was a predictor of recurrence in adrenocortical carcinomas. |
| doi_str_mv | 10.18632/oncotarget.4261 |
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Recently, hot-spot DICER1 mutations were found in ovarian tumors, and TARBP2 truncating mutations in tumor cell lines with microsatellite instability. In this study, we assessed DICER1 e TRBP protein expression in 154 adult adrenocortical tumors (75 adenomas and 79 carcinomas). Expression of DICER1 and TARBP2 gene was assessed in a subgroup of 61 tumors. Additionally, we investigated mutations in metal biding sites located at the RNase IIIb domain of DICER1 and in the exon 5 of TARBP2 in 61 tumors. A strong DICER1 expression was demonstrated in 32% of adenomas and in 51% of carcinomas (p = 0.028). Similarly, DICER1 gene overexpression was more frequent in carcinomas (60%) than in adenomas (23%, p = 0.006). But, among adrenocortical carcinomas, a weak DICER1 expression was significantly more frequent in metastatic than in non-metastatic adrenocortical carcinomas (66% vs. 31%; p = 0.002). Additionally, a weak DICER1 expression was significantly correlated with a reduced overall (p = 0.004) and disease-free (p = 0.005) survival. In the multivariate analysis, a weak DICER1 expression (p = 0.048) remained as independent predictor of recurrence. Regarding TARBP2 gene, its protein and gene expression did not correlate with histopathological and clinical parameters. No variant was identified in hot spot areas of DICER1 and TARBP2. In conclusion, a weak DICER1 protein expression was associated with reduced disease-free and overall survival and was a predictor of recurrence in adrenocortical carcinomas.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.4261</identifier><identifier>PMID: 26087193</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Adenoma - genetics ; Adenoma - metabolism ; Adenoma - pathology ; Adolescent ; Adrenal Cortex Neoplasms - genetics ; Adrenal Cortex Neoplasms - metabolism ; Adrenal Cortex Neoplasms - pathology ; Adrenocortical Carcinoma - genetics ; Adrenocortical Carcinoma - metabolism ; Adrenocortical Carcinoma - pathology ; Adult ; Aged ; DEAD-box RNA Helicases - biosynthesis ; DEAD-box RNA Helicases - genetics ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Male ; Middle Aged ; Research Paper ; Ribonuclease III - biosynthesis ; Ribonuclease III - genetics ; RNA-Binding Proteins - biosynthesis ; RNA-Binding Proteins - genetics ; Survival Analysis ; Treatment Outcome ; Young Adult</subject><ispartof>Oncotarget, 2015-09, Vol.6 (26), p.22724-22733</ispartof><rights>Copyright: © 2015 de Sousa et al. 2015</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-2528245e4cd9c5a01fb11e5a2352ffc8479c36998e6c7121778b2cc4b7cdc78c3</citedby><cites>FETCH-LOGICAL-c396t-2528245e4cd9c5a01fb11e5a2352ffc8479c36998e6c7121778b2cc4b7cdc78c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673194/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673194/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,733,786,790,891,27957,27958,53827,53829</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26087193$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Sousa, Gabriela Resende Vieira</creatorcontrib><creatorcontrib>Ribeiro, Tamaya C</creatorcontrib><creatorcontrib>Faria, Andre M</creatorcontrib><creatorcontrib>Mariani, Beatriz M P</creatorcontrib><creatorcontrib>Lerario, Antonio M</creatorcontrib><creatorcontrib>Zerbini, Maria Claudia N</creatorcontrib><creatorcontrib>Soares, Iberê C</creatorcontrib><creatorcontrib>Wakamatsu, Alda</creatorcontrib><creatorcontrib>Alves, Venancio A F</creatorcontrib><creatorcontrib>Mendonca, Berenice B</creatorcontrib><creatorcontrib>Fragoso, Maria Candida B V</creatorcontrib><creatorcontrib>Latronico, Ana Claudia</creatorcontrib><creatorcontrib>Almeida, Madson Q</creatorcontrib><title>Low DICER1 expression is associated with poor clinical outcome in adrenocortical carcinoma</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Low DICER1 expression was associated with poor outcome in several cancers. Recently, hot-spot DICER1 mutations were found in ovarian tumors, and TARBP2 truncating mutations in tumor cell lines with microsatellite instability. In this study, we assessed DICER1 e TRBP protein expression in 154 adult adrenocortical tumors (75 adenomas and 79 carcinomas). Expression of DICER1 and TARBP2 gene was assessed in a subgroup of 61 tumors. Additionally, we investigated mutations in metal biding sites located at the RNase IIIb domain of DICER1 and in the exon 5 of TARBP2 in 61 tumors. A strong DICER1 expression was demonstrated in 32% of adenomas and in 51% of carcinomas (p = 0.028). Similarly, DICER1 gene overexpression was more frequent in carcinomas (60%) than in adenomas (23%, p = 0.006). But, among adrenocortical carcinomas, a weak DICER1 expression was significantly more frequent in metastatic than in non-metastatic adrenocortical carcinomas (66% vs. 31%; p = 0.002). Additionally, a weak DICER1 expression was significantly correlated with a reduced overall (p = 0.004) and disease-free (p = 0.005) survival. In the multivariate analysis, a weak DICER1 expression (p = 0.048) remained as independent predictor of recurrence. Regarding TARBP2 gene, its protein and gene expression did not correlate with histopathological and clinical parameters. No variant was identified in hot spot areas of DICER1 and TARBP2. In conclusion, a weak DICER1 protein expression was associated with reduced disease-free and overall survival and was a predictor of recurrence in adrenocortical carcinomas.</description><subject>Adenoma - genetics</subject><subject>Adenoma - metabolism</subject><subject>Adenoma - pathology</subject><subject>Adolescent</subject><subject>Adrenal Cortex Neoplasms - genetics</subject><subject>Adrenal Cortex Neoplasms - metabolism</subject><subject>Adrenal Cortex Neoplasms - pathology</subject><subject>Adrenocortical Carcinoma - genetics</subject><subject>Adrenocortical Carcinoma - metabolism</subject><subject>Adrenocortical Carcinoma - pathology</subject><subject>Adult</subject><subject>Aged</subject><subject>DEAD-box RNA Helicases - biosynthesis</subject><subject>DEAD-box RNA Helicases - genetics</subject><subject>Disease Progression</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Research Paper</subject><subject>Ribonuclease III - biosynthesis</subject><subject>Ribonuclease III - genetics</subject><subject>RNA-Binding Proteins - biosynthesis</subject><subject>RNA-Binding Proteins - genetics</subject><subject>Survival Analysis</subject><subject>Treatment Outcome</subject><subject>Young Adult</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNpVUU1LBDEMLaKorN49SY9eVqftzLS9CLKuH7AgiF68lG6mo5WZZm27fvx7x_U7hyTwkpdHHiF7rDhkqhb8CANgtvHe5cOS12yNbDNd6jGvKrH-p98iuyk9FkNUpVRcb5ItXhdKMi22yd0MX-jp5WR6zah7XUSXksdAfaI2JQRvs2voi88PdIEYKXQ-eLAdxWUG7B31gdomuoCAMa8QsBF8wN7ukI3WdsntftURuT2b3kwuxrOr88vJyWwMQtd5kMgVLytXQqOhsgVr54y5ynJR8bYFVUoNotZauRok40xKNecA5VxCA1KBGJHjT97Fct67BlzI0XZmEX1v45tB681_JPgHc4_PpqylGL40EBx8EUR8WrqUTe8TuK6zweEyGSZZpYek1DBafI5CxJSia3_OsMKsXDG_rpgPV4aV_b_yfha-PRDvwrSM9Q</recordid><startdate>20150908</startdate><enddate>20150908</enddate><creator>de Sousa, Gabriela Resende Vieira</creator><creator>Ribeiro, Tamaya C</creator><creator>Faria, Andre M</creator><creator>Mariani, Beatriz M P</creator><creator>Lerario, Antonio M</creator><creator>Zerbini, Maria Claudia N</creator><creator>Soares, Iberê C</creator><creator>Wakamatsu, Alda</creator><creator>Alves, Venancio A F</creator><creator>Mendonca, Berenice B</creator><creator>Fragoso, Maria Candida B V</creator><creator>Latronico, Ana Claudia</creator><creator>Almeida, Madson Q</creator><general>Impact Journals LLC</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150908</creationdate><title>Low DICER1 expression is associated with poor clinical outcome in adrenocortical carcinoma</title><author>de Sousa, Gabriela Resende Vieira ; 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Recently, hot-spot DICER1 mutations were found in ovarian tumors, and TARBP2 truncating mutations in tumor cell lines with microsatellite instability. In this study, we assessed DICER1 e TRBP protein expression in 154 adult adrenocortical tumors (75 adenomas and 79 carcinomas). Expression of DICER1 and TARBP2 gene was assessed in a subgroup of 61 tumors. Additionally, we investigated mutations in metal biding sites located at the RNase IIIb domain of DICER1 and in the exon 5 of TARBP2 in 61 tumors. A strong DICER1 expression was demonstrated in 32% of adenomas and in 51% of carcinomas (p = 0.028). Similarly, DICER1 gene overexpression was more frequent in carcinomas (60%) than in adenomas (23%, p = 0.006). But, among adrenocortical carcinomas, a weak DICER1 expression was significantly more frequent in metastatic than in non-metastatic adrenocortical carcinomas (66% vs. 31%; p = 0.002). Additionally, a weak DICER1 expression was significantly correlated with a reduced overall (p = 0.004) and disease-free (p = 0.005) survival. In the multivariate analysis, a weak DICER1 expression (p = 0.048) remained as independent predictor of recurrence. Regarding TARBP2 gene, its protein and gene expression did not correlate with histopathological and clinical parameters. No variant was identified in hot spot areas of DICER1 and TARBP2. In conclusion, a weak DICER1 protein expression was associated with reduced disease-free and overall survival and was a predictor of recurrence in adrenocortical carcinomas.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>26087193</pmid><doi>10.18632/oncotarget.4261</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenoma - genetics Adenoma - metabolism Adenoma - pathology Adolescent Adrenal Cortex Neoplasms - genetics Adrenal Cortex Neoplasms - metabolism Adrenal Cortex Neoplasms - pathology Adrenocortical Carcinoma - genetics Adrenocortical Carcinoma - metabolism Adrenocortical Carcinoma - pathology Adult Aged DEAD-box RNA Helicases - biosynthesis DEAD-box RNA Helicases - genetics Disease Progression Disease-Free Survival Female Humans Male Middle Aged Research Paper Ribonuclease III - biosynthesis Ribonuclease III - genetics RNA-Binding Proteins - biosynthesis RNA-Binding Proteins - genetics Survival Analysis Treatment Outcome Young Adult |
| title | Low DICER1 expression is associated with poor clinical outcome in adrenocortical carcinoma |
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