Focal DNA methylation measurement in adrenocortical carcinoma is a prognostic marker independent from tumor stage and Ki67; an ENSAT study

2016 ◽  
Author(s):  
Guillaume Assie ◽  
Anne Jouinot ◽  
Rossella Libe ◽  
Martin Fassnacht ◽  
Silviu Sbiera ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Prognostic Marker ◽  
Adrenocortical Carcinoma ◽  
Tumor Stage

Pathological and Genetic Stratification for Management of Adrenocortical Carcinoma

2021 ◽  
Author(s):  
Michael R Clay ◽  
Emilia M Pinto ◽  
Lauren Fishbein ◽  
Tobias Else ◽  
Katja Kiseljak-Vassiliades
Keyword(s):  
Adrenocortical Carcinoma ◽  
Therapeutic Approach ◽  
Evidence Synthesis ◽  
Critical Role ◽  
Tumor Stage ◽  
Significant Heterogeneity ◽  
Clinical Predictors ◽  
Comprehensive Genomic Profiling ◽  
Pubmed Search ◽  
Genetic Stratification

Abstract Context Adrenocortical carcinoma (ACC) is a rare endocrine malignancy that affects patients across the age spectrum. Although the overall survival in patients with ACC is poor, there is significant heterogeneity in terms of outcomes, presentation, and underlying genetic drivers. Evidence Acquisition This review is based on the evidence collected from primary research studies, expert reviews, and published guidelines. The studies were identified through PubMed search with key words “adrenocortical carcinoma”, “prognosis”, “pathology” and “genetics”. The PubMed search was complemented by authors’ expertise, research, and clinical experience in the field of ACC. Evidence Synthesis Identification of biomarkers has been critical to gain better insight into tumor behavior and to guide therapeutic approach to patients. Tumor stage, resection status and Ki67 are pathological tumor characteristics that have been identified as prognosticators in patients with ACC. Cortisol excess also correlates with worse prognosis. Clinical and histopathological characteristics help stratify patient outcomes, yet still up to 25% of patients have a different outcome than predicted. To bridge this gap, comprehensive genomic profiling studies have characterized additional profiles that correlate with clinical outcomes. In addition, studies of clinically applicable molecular markers are underway to further stratify outcomes in patients with ACC tumors. Conclusions Clinical predictors in combination with pathological markers play a critical role in the approach to patients with ACC. Recent advances in genetic prognosticators will help extend the stratification of these tumors and contribute to a personalized therapeutic approach to patients with ACC.

scholarly journals Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3411
Author(s):  
Laura Pignata ◽  
Orazio Palumbo ◽  
Flavia Cerrato ◽  
Basilia Acurzio ◽  
Enrique de Álava ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Chromosome Aberrations ◽  
Wilms Tumor ◽  
Tumor Stage ◽  
Copy Number Variations ◽  
Molecular Defect ◽  
Driver Genes ◽  
Cancer Driver ◽  
Aggressive Tumors ◽  
Methylation Defects

The embryonal renal cancer Wilms tumor (WT) accounts for 7% of all children’s malignancies. Its most frequent molecular defect is represented by DNA methylation abnormalities at the imprinted 11p15.5 region. Multiple imprinted methylation alterations dictated by chromosome copy-number variations have been recently demonstrated in adult cancers, raising the question of whether multiple imprinted loci were also affected in WT. To address this issue, we analyzed DNA methylation and chromosome profiles of 7 imprinted loci in 48 WT samples. The results demonstrated that methylation abnormalities of multiple imprinted loci occurred in 35% of the cases, but that they were associated with either chromosome aberrations or normal chromosome profiles. Multiple imprinted methylation changes were correlated with tumor stage and presence of metastasis, indicating that these epimutations were more frequent in highly aggressive tumors. When chromosome profiles were affected, these alterations were extended to flanking cancer driver genes. Overall, this study demonstrates the presence of multiple imprinted methylation defects in aggressive WTs and suggests that the mechanism by which they arise in embryonal and adult cancers is different.

THE IMPACT OF TUMOR STAGE ON PROGNOSIS IN CHILDREN WITH ADRENOCORTICAL CARCINOMA

2005 ◽  
Vol 174 (6) ◽  
pp. 2338-2342 ◽  
Author(s):  
SILVIO TUCCI ◽  
ANTONIO C.P. MARTINS ◽  
HAYLTON J. SUAID ◽  
ADAUTO J. COLOGNA ◽  
RODOLFO B. REIS
Keyword(s):  
Adrenocortical Carcinoma ◽  
Tumor Stage ◽  
The Impact

scholarly journals Serum RARRES2 Is a Prognostic Marker in Patients With Adrenocortical Carcinoma

2016 ◽  
Vol 101 (9) ◽  
pp. 3345-3352 ◽  
Author(s):  
Yi Liu-Chittenden ◽  
Dhaval Patel ◽  
Kelli Gaskins ◽  
Thomas J. Giordano ◽  
Guillaume Assie ◽  
...  
Keyword(s):  
Prognostic Marker ◽  
Adrenocortical Carcinoma

scholarly journals Prognostic and Monitoring Value of Circulating Tumor Cells in Adrenocortical Carcinoma: A Preliminary Monocentric Study

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3176
Author(s):  
Giulia Cantini ◽  
Letizia Canu ◽  
Roberta Armignacco ◽  
Francesca Salvianti ◽  
Giuseppina De Filpo ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Adrenocortical Carcinoma ◽  
Tumor Stage ◽  
Median Number ◽  
Tumor Evolution ◽  
Blood Draw ◽  
Post Surgery ◽  
Small Cohort ◽  
Tumor Material

Adrenocortical carcinoma (ACC), a rare and aggressive neoplasia, presents poor prognosis when metastatic at diagnosis and limited therapies are available. Specific and sensitive markers for early diagnosis and a monitoring system of therapy and tumor evolution are urgently needed. The liquid biopsy represents a source of tumor material within a minimally invasive blood draw that allows the recovery of circulating tumor cells (CTCs). CTCs have been recently shown to be detectable in ACC. In the present paper, we evaluated the prognostic value of CTCs obtained by size-filtration in a small pilot cohort of 19 ACC patients. We found CTCs in 68% of pre-surgery and in 38% of post-surgery blood samples. In addition, CTC clusters (CTMs) and cancer associated macrophages (CAMLs) were detectable in some ACC patients. The median number of CTCs significantly decreased after the mass removal. Finally, stratifying patients in high and low pre-surgery CTC number groups, assuming the 75th percentile CTC value as cut-off, CTCs significantly predicted patients’ overall survival (log rank = 0.005), also in a multivariate analysis adjusted for age and tumor stage. In conclusion, though preliminary and performed in a small cohort of patients, our study suggests that CTC number may represent a promising marker for prognosis and disease monitoring in ACC.

Genome‐wide investigation of intragenic DNA methylation identifies ZMIZ1 gene as a prognostic marker in glioblastoma and multiple cancer types

2019 ◽  
Vol 145 (12) ◽  
pp. 3425-3435 ◽  
Author(s):  
Dimitrios Mathios ◽  
Taeyoung Hwang ◽  
Yuanxuan Xia ◽  
Jillian Phallen ◽  
Yuan Rui ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Prognostic Marker ◽  
Multiple Cancer ◽  
Genome Wide ◽  
Cancer Types

Induction of an aggressive phenotype and poor survival in early-stage lung adenocarcinoma and epigenetic inactivation of microRNA-34b/c.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11056-11056
Author(s):  
Ernest Nadal ◽  
Marc Gallegos ◽  
Guoan Chen ◽  
Ramon Palmero ◽  
Gabriel Capella ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Lung Adenocarcinoma ◽  
Prognostic Marker ◽  
Cell Lines ◽  
Early Stage ◽  
Migration And Invasion ◽  
Primary Tumors ◽  
Epigenetic Inactivation ◽  
Aggressive Phenotype ◽  
Independent Prognostic Marker

11056 Background: The microRNA-34b/c (miR-34b/c) is a transcriptional target of TP53 that is frequently mutated in primary lung adenocarcinoma (AC). We investigated the clinical implications of miR-34b/c methylation in early stage lung AC patients and the functional role of miR-34b/c re-expression in lung AC cell lines. Methods: DNA methylation of miR-34b/c promoter was assessed by real-time PCR temperature dissociation in 15 lung AC cell lines and 140 early stage lung AC resected at the Bellvitge Hospital (Barcelona) and at the University of Michigan (Ann Arbor). Patient characteristics: 65% males, 88% smokers, 68.5% stage I and 31.5% stage II. Expression of miR-34b/c was determined by TaqMan RT-PCR. Two lung AC cell lines (NCI-H1838 and SK-LU-1) were transfected with an expression vector containing both miRs and the effects upon cell proliferation, migration and invasion were determined. Results: MiR-34b/c was methylated in 40% of cell lines and in 46% of primary tumors with significant association with higher tumor stage (P=0.033), recurrence (P=0.017) and death (P=0.005). In the training set (n=58), patients with higher levels of miR-34b/c methylation had significantly shorter median DFS (28.5 months) compared to low to medium levels (not reached, log-rank P=0.016). In the test set (n=82), higher levels of miR-34b/c methylation were also associated to shorter median DFS (19 months) compared to patients with low to medium levels (not reached, log-rank P=0.005). MiR-34b/c methylation remained an independent prognostic marker for DFS after adjusting by age, gender and stage. Tumors harboring TP53 mutations and miR-34b/c methylation expressed significantly lower levels of miR-34b/c (P≤0.001). Stable cells expressing miR-34b/c had lower proliferation rate relative to cells transfected with empty vector (P≤0.001). Expressing miR-34b/c in SK-LU-1 cells reduced migration and invasion ability. Conclusions: Epigenetic inactivation of miR-34b/c by DNA methylation is an independent prognostic marker in early stage lung AC. Ectopic expression of miR-34b/c generated a less aggressive phenotype in lung AC cell lines suggesting a potential for therapeutic targeting.

scholarly journals DNA Methylation Changes Correlate with Gleason Score and Tumor Stage in Prostate Cancer

2012 ◽  
Vol 31 (2) ◽  
pp. 187-192 ◽  
Author(s):  
Lissette Delgado-Cruzata ◽  
Gregory W. Hruby ◽  
Karina Gonzalez ◽  
James McKiernan ◽  
Mitchel C. Benson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Methylation ◽  
Gleason Score ◽  
Tumor Stage
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