Gene Expression Profiling Reveals a New Classification of Adrenocortical Tumors and Identifies Molecular Predictors of Malignancy and Survival

Reyniès, Aurélien de; Assié, Guillaume; Rickman, David S.; Tissier, Frédérique; Groussin, Lionel; René-Corail, Fernande; Dousset, B.; Bertagna, Xavier; Clauser, Éric; Bertherat, Jérôme

doi:10.1200/jco.2008.18.5678

Cited by 334 publications

(388 citation statements)

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“…Overexpression of several genes involved in the regulation of G2/M phase transition was noted in ACCs and correlated with chromosome gains: CCNB1 and cell division protein kinase 7 (CDK7) on chr5q13, ubiquitin C (UBC) on chr12q24, and Mdm2 p53-binding protein homologue (MDM2) on chr12q15 (Giordano et al, 2003(Giordano et al, , 2009To¨mbo¨l et al, 2009;de Reynie`s et al, 2009). Overexpression of CCNB1 in ACCs was validated in the recent study by Soon et al (2009) as well.…”

Section: Cell Cyclementioning

confidence: 88%

“…Several other members of G2/M transition were significantly overexpressed in ACCs without corresponding chromosomal alterations in at least three microarray studies, including CCNB2, CDC2, CDC25B and topoisomerase II alpha (TOP2A) (Giordano et al, 2003(Giordano et al, , 2009To¨mbo¨l et al, 2009;Soon et al, 2009;de Reynie`s et al, 2009). Overexpression of TOP2A has already been reported and considered as a diagnostic marker for ACCs (Giordano et al, 2003).…”

Section: Cell Cyclementioning

confidence: 96%

“…Overexpression G1 cyclins (cyclin E), and G1 cell division protein kinases (CDK2, CDK4) was reported in sporadic ACCs (Bourcigaux et al, 2000). Overexpression of CCNE1 and CCNE2 was found in four of the investigated microarray studies (Giordano et al, 2003(Giordano et al, , 2009To¨mbo¨l et al, 2009;de Reynie`s et al, 2009). GSEA of microarray studies revealed significant enrichment of overexpressed genes on chr19q12, where CCNE1 is mapped (Giordano et al, 2009;To¨mbo¨l et al, 2009;de Reynie`s et al, 2009).…”

Section: Cell Cyclementioning

confidence: 99%

“…It is of interest to note that C-MYC overexpressed in several other tumours was found to be underexpressed in three microarray data sets analysed (Giordano et al, 2009;To¨mbo¨l et al, 2009;de Reynie`s et al, 2009). In our direct comparison of CGH and GSEA results, its underexpression was correlated with loss of chr8q24, where C-MYC is harboured.…”

Section: Cell Cyclementioning

confidence: 99%

“…Gene expression alterations may be used for the differentiation of benign and malignant tumours (de Fraipont et al, 2005;Soon et al, 2009) and for determining ACC prognosis (de Reynie`s et al, 2009). Beside steady alterations observed in all settings (for example, overexpression of IGF-2 mRNA in ACC), considerable differences can be found in different studies.…”

Section: Introductionmentioning

confidence: 99%

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Meta-analysis of adrenocortical tumour genomics data: novel pathogenic pathways revealed

et al. 2010

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Section: Cell Cyclementioning

confidence: 88%

Section: Cell Cyclementioning

confidence: 96%

Section: Cell Cyclementioning

confidence: 99%

Section: Cell Cyclementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Meta-analysis of adrenocortical tumour genomics data: novel pathogenic pathways revealed

et al. 2010

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Value of Molecular Classification for Prognostic Assessment of Adrenocortical Carcinoma

et al. 2019

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The risk stratification of adrenocortical carcinoma (ACC) based on tumor proliferation index and stage is limited. Adjuvant therapy after surgery is recommended for most patients. Pan-genomic studies have identified distinct molecular groups closely associated with outcome. OBJECTIVE To compare the molecular classification for prognostic assessment of ACC with other known prognostic factors. DESIGN, SETTING, AND PARTICIPANTS In this retrospective biomarker analysis, ACC tumor samples from 368 patients who had undergone surgical tumor removal were collected from March 1, 2005, to September 30, 2015 (144 in the training cohort and 224 in the validation cohort) at 21 referral centers with a median follow-up of 35 months (interquartile range, 18-74 months). Data were analyzed from March 2016 to March 2018. EXPOSURES Meta-analysis of pan-genomic studies (transcriptome, methylome, chromosome alteration, and mutational profiles) was performed on the training cohort. Targeted biomarker analysis, including targeted gene expression (BUB1B and PINK1), targeted methylation (PAX5, GSTP1, PYCARD, and PAX6), and targeted next-generation sequencing, was performed on the training and validation cohorts. MAIN OUTCOMES AND MEASURES Disease-free survival. Cox proportional hazards regression and C indexes were used to assess the prognostic value of each model. RESULTS Of the 368 patients (mean [SD] age, 49 [16] years), 144 were in the training cohort (100 [69.4%] female) and 224 were in the validation cohort (142 [63.4%] female). In the training cohort, pan-genomic measures classified ACC into 3 molecular groups (A1, A2, and A3-B), with 5-year survival of 9% for group A1, 45% for group A2, and 82% for group A3-B (log-rank P < .001). Molecular class was an independent prognostic factor of recurrence in stage I to III ACC after complete surgery (hazard ratio, 55.91; 95% CI, 8.55-365.40; P < .001). The combination of European Network for the Study of Adrenal Tumors (ENSAT) stage, tumor proliferation index, and molecular class provided the most discriminant prognostic model (C index, 0.88). In the validation cohort, the molecular classification, determined by targeted biomarker measures, was confirmed as an independent prognostic factor of recurrence (hazard ratio, 5.96 [95% CI, 1.81-19.58], P = .003 for the targeted classifier combining expression, methylation, and chromosome alterations; and 2.61 [95% CI, 1.31-5.19], P = .006 for the targeted classifier combining methylation, chromosome alterations, and mutational profile). The prognostic value of the molecular markers was limited for patients with stage IV ACC. CONCLUSIONS AND RELEVANCE The findings suggest that in localized ACC, targeted classifiers may be used as independent markers of recurrence. The determination of molecular class may improve individual prognostic assessment and thus may spare unnecessary adjuvant treatment.

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MicroRNA profiling of adrenocortical tumors reveals miR‐483 as a marker of malignancy

Patterson

Holloway

Weng

et al. 2010

Cancer

155

172

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BACKGROUND:The authors are interested in identifying molecular markers that can aid in the diagnosis of adrenocortical carcinoma (ACC). The aim of this study was to identify microRNAs (miRNAs or miRs) that are differentially expressed in malignant adrenocortical tumors as compared with benign tumors and assess their potential as diagnostic predictors.METHODS:Differentially expressed miRNAs were identified using microarray profiling of adrenocortical tumors and validated by quantitative real‐time RT‐PCR.RESULTS:Microarray profiling in benign and primary malignant adrenocortical tumors revealed several significant differences between these histological groups. By using directed quantitative RT‐PCR analysis on a subset of these differentially expressed miRNAs, the authors determined that miRs ‐100, ‐125b, and ‐195 were significantly down‐regulated, whereas miR‐483‐5p was significantly up‐regulated in malignant as compared with benign tumors. Furthermore, the current study shows that miR‐483‐5p expression can accurately categorize tumors as benign or malignant.CONCLUSIONS:The authors identified 4 miRNAs that are dysregulated in adrenocortical carcinoma. The high expression of one of these, miR‐483‐5p, appears to be a defining characteristic of adrenocortical malignancies, and can thus be used to accurately distinguish between benign and malignant adrenocortical tumors. Cancer 2011. © 2010 American Cancer Society.

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Gene Expression Profiling Reveals a New Classification of Adrenocortical Tumors and Identifies Molecular Predictors of Malignancy and Survival

Cited by 334 publications

References 41 publications

Meta-analysis of adrenocortical tumour genomics data: novel pathogenic pathways revealed

Meta-analysis of adrenocortical tumour genomics data: novel pathogenic pathways revealed

Value of Molecular Classification for Prognostic Assessment of Adrenocortical Carcinoma

MicroRNA profiling of adrenocortical tumors reveals miR‐483 as a marker of malignancy

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