Evidence map›Paper›PMID 32698135›Full record

ArticleEndocrine connections2020

Intratumor heterogeneity of prognostic DNA-based molecular markers in adrenocortical carcinoma.

Anne Jouinot, Juliane Lippert, Martin Fassnacht, Bruno de La Villeon, Amandine Septier, Mario Neou, Karine Perlemoine, Silke Appenzeller, Mathilde Sibony, Sébastien Gaujoux and 6 more

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Anne JouinotUniversité de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France.
Juliane LippertDepartment of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Wuerzburg, Wuerzburg, Germany.
Martin FassnachtDepartment of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Wuerzburg, Wuerzburg, Germany.
Bruno de La VilleonUniversité de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France.
Amandine SeptierUniversité de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France.
Mario NeouUniversité de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France.
Karine PerlemoineUniversité de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France.
Silke AppenzellerDepartment of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Wuerzburg, Wuerzburg, Germany.
Mathilde SibonyUniversité de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France.
Sébastien GaujouxUniversité de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France.
Bertrand DoussetUniversité de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France.
Rossella LibeUniversité de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France.
Lionel GroussinUniversité de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France.
Cristina L RonchiDepartment of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Wuerzburg, Wuerzburg, Germany.
Guillaume AssiéUniversité de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France.
Jérôme BertheratUniversité de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

adrenocortical carcinomachromosome alterationsintratumor heterogeneitymethylationsomatic mutations

Identifiers

PMID32698135
PMCPMC7424337

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