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. 2020 Nov 10;8(1):190.
doi: 10.1186/s40478-020-01067-5.

Chromosomal instability in the prediction of pituitary neuroendocrine tumors prognosis

Hélène Lasolle  1   2   3 , Mad-Hélénie Elsensohn  2   4   5 , Anne Wierinckx  2   4   6 , Eudeline Alix  7 , Clément Bonnefille  7 , Alexandre Vasiljevic  2   3   8 , Christine Cortet  9 , Bénédicte Decoudier  10 , Nathalie Sturm  11 , Stephan Gaillard  12 , Amandine Ferrière  13   14 , Pascal Roy  2   4   5 , Emmanuel Jouanneau  2   3   15 , Philippe Bertolino  3 , Claire Bardel  2   4   5   16 , Damien Sanlaville  2   7   16 , Gérald Raverot  17   18   19
Affiliations

Chromosomal instability in the prediction of pituitary neuroendocrine tumors prognosis

Hélène Lasolle et al. Acta Neuropathol Commun. .

Abstract

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.

Keywords: Copy number variations; Genomic instability; Pituitary adenoma; Pituitary neuroendocrine tumors; Prognosis.

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Conflict of interest statement

The authors declare no potential conflicts of interest.

Figures

Fig. 1
Fig. 1
Barplot of the quantities of altered probes per tumor
Fig. 2
Fig. 2
Boxplot of the quantities of altered, deleted and gained probes per tumor type
Fig. 3
Fig. 3
Heatmap of the non-hierarchical clustering in the whole cohort
Fig. 4
Fig. 4
Heatmap representation of the CNV in each tumor type
See this image and copyright information in PMC

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