ArticleEndocrine connections2020
Intratumor heterogeneity of prognostic DNA-based molecular markers in adrenocortical carcinoma.
Article in Endocrine connections, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Genomic Catastrophe Defines the Evolutionary Trajectory of Adrenocortical Carcinoma.Endocrine pathology · 2026Article
- Article
- Update on Biology and Genomics of Adrenocortical Carcinomas: Rationale for Emerging Therapies.Endocrine reviews · 2022Article
- Prognostic Role of Targeted Methylation Analysis in Paraffin-embedded Samples of Adrenocortical Carcinoma.The Journal of clinical endocrinology and metabolism · 2022Article
- Transcriptome in paraffin samples for the diagnosis and prognosis of adrenocortical carcinoma.European journal of endocrinology · 2022Article
- Molecular genotyping of adrenocortical carcinoma: a systematic analysis of published literature 2019-2021.Current opinion in oncology · 2022Review
- What Did We Learn from the Molecular Biology of Adrenal Cortical Neoplasia? From Histopathology to Translational Genomics.Endocrine pathology · 2021Review
- The Role of Biomarkers in Adrenocortical Carcinoma: A Review of Current Evidence and Future Perspectives.Biomedicines · 2021Review
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16 authors.
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Abstract
backgroundThe prognosis of adrenocortical carcinoma (ACC) is heterogeneous. Genomic studies have identified ACC subgroups characterized by specific molecular alterations, including features measured at DNA level (somatic mutations, chromosome alterations, DNA methylation), which are closely associated with outcome. The aim of this study was to evaluate intratumor heterogeneity of prognostic molecular markers at the DNA level.
methodsTwo different tissue samples (primary tumor, local recurrence or metastasis) were analyzed in 26 patients who underwent surgery for primary or recurrent ACC. DNA-related biomarkers with prognostic role were investigated in frozen and paraffin-embedded samples. Somatic mutations of p53/Rb and Wnt/β-catenin pathways were assessed using next-generation sequencing (n = 26), chromosome alteration profiles were determined using SNP arrays (n = 14) and methylation profiles were determined using four-gene bisulfite pyrosequencing (n = 12).
resultsSomatic mutations for ZNRF3, TP53, CTNN1B and CDKN2A were found in 7, 6, 6 and 4 patients, respectively, with intratumor heterogeneity in 8/26 patients (31%). Chromosome alteration profiles were 'Noisy' (numerous and anarchic alterations) in 8/14 and 'Chromosomal' (extended patterns of loss of heterozygosity) in 5/14 of the study samples. For these profiles, no intratumor heterogeneity was observed. Methylation profiles were hypermethylated in 5/12 and non-hypermethylated in 7/12 of the study samples. Intratumor heterogeneity of methylation profiles was observed in 2/12 patients (17%).
conclusionsIntratumor heterogeneity impacts DNA-related molecular markers. While somatic mutation can differ, prognostic DNA methylation and chromosome alteration profile seem rather stable and might be more robust for the prognostic assessment.
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