Chromosomal instability in the prediction of pituitary neuroendocrine tumors prognosis
| العنوان: | Chromosomal instability in the prediction of pituitary neuroendocrine tumors prognosis |
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| المؤلفون: | Lasolle, Hélène, Elsensohn, Mad-Hélénie, Wierinckx, Anne, Alix, Eudeline, Bonnefille, Clément, Vasiljevic, Alexandre, Cortet, Christine, Decoudier, Bénédicte, Sturm, Nathalie, Gaillard, Stephan, Ferrière, Amandine, Roy, Pascal, Jouanneau, Emmanuel, Bertolino, Philippe, Bardel, Claire, Sanlaville, Damien, Raverot, Gérald |
| المصدر: | Acta Neuropathologica Communications Acta Neuropathologica Communications, Vol 8, Iss 1, Pp 1-14 (2020) |
| بيانات النشر: | BioMed Central, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Genomic instability, Adenoma, Adult, Male, endocrine system, DNA Copy Number Variations, Loss of Heterozygosity, Gonadotrophs, lcsh:RC346-429, Chromosomal Instability, Endopeptidases, Chromogranins, GTP-Binding Protein alpha Subunits, Gs, Humans, Pituitary Neoplasms, Prolactinoma, Copy number variations, lcsh:Neurology. Diseases of the nervous system, Comparative Genomic Hybridization, Endosomal Sorting Complexes Required for Transport, Research, Gene Expression Profiling, Pituitary neuroendocrine tumors, Middle Aged, Prognosis, Pituitary adenoma, Neuroendocrine Tumors, ACTH-Secreting Pituitary Adenoma, Mutation, Female, Growth Hormone-Secreting Pituitary Adenoma, Neoplasm Recurrence, Local, Ubiquitin Thiolesterase |
| الوصف: | The purpose of this study was to analyze the impact of copy number variations (CNV) on sporadic pituitary neuroendocrine tumors (PitNETs) prognosis, to identify specific prognosis markers according to the known clinico-pathological classification. CGH array analysis was performed on 195 fresh-frozen PitNETs (56 gonadotroph, 11 immunonegative, 56 somatotroph, 39 lactotroph and 33 corticotroph), with 5 years post-surgery follow-up (124 recurrences), classified according to the five-tiered grading classification (invasion, Ki-67, mitotic index and p53 positivity). Effect of alterations on recurrence was studied using logistic regression models. Transcriptomic analysis of 32 lactotroph tumors was performed. The quantity of CNV was dependent on tumor type: higher in lactotroph (median(min–max) = 38% (0–97) of probes) compared to corticotroph (11% (0–77)), somatotroph (5% (0–99)), gonadotroph (0% (0–10)) and immunonegative tumors (0% (0–17). It was not predictive of recurrence in the whole cohort. In lactotroph tumors, genome instability, especially quantity of gains, significantly predicted recurrence independently of invasion and proliferation (p-value = 0.02, OR = 1.2). However, no specific CNV was found as a prognostic marker. Transcriptomic analysis of the genes included in the CNV and associated with prognosis didn’t show significantly overrepresented pathway. In somatotroph and corticotroph tumors, USP8 and GNAS mutations were not associated with genome disruption or recurrence respectively. To conclude, CGH array analysis showed genome instability was dependent on PitNET type. Lactotroph tumors were highly altered and the quantity of altered genome was associated with poorer prognosis though the mechanism is unclear, whereas gonadotroph and immunonegative tumors showed the same ‘quiet’ profile, leaving the mechanism underlying tumorigenesis open to question. Electronic supplementary material The online version of this article (10.1186/s40478-020-01067-5) contains supplementary material, which is available to authorized users. |
| اللغة: | English |
| تدمد: | 2051-5960 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::18b462bc9d52116fe78ed6ad48ca70e1Test http://europepmc.org/articles/PMC7653703Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....18b462bc9d52116fe78ed6ad48ca70e1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20515960 |
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