Ontology type: schema:ScholarlyArticle Open Access: True
2020-11-10
AUTHORSHélène Lasolle, Mad-Hélénie Elsensohn, Anne Wierinckx, Eudeline Alix, Clément Bonnefille, Alexandre Vasiljevic, Christine Cortet, Bénédicte Decoudier, Nathalie Sturm, Stephan Gaillard, Amandine Ferrière, Pascal Roy, Emmanuel Jouanneau, Philippe Bertolino, Claire Bardel, Damien Sanlaville, Gérald Raverot
ABSTRACTThe 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. More... »
PAGES190
http://scigraph.springernature.com/pub.10.1186/s40478-020-01067-5
DOIhttp://dx.doi.org/10.1186/s40478-020-01067-5
DIMENSIONShttps://app.dimensions.ai/details/publication/pub.1132463880
PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/33168091
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"description": "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\u00a0years 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\u2013max)\u2009=\u200938% (0\u201397) of probes) compared to corticotroph (11% (0\u201377)), somatotroph (5% (0\u201399)), gonadotroph (0% (0\u201310)) and immunonegative tumors (0% (0\u201317). 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\u2009=\u20090.02, OR\u2009=\u20091.2). However, no specific CNV was found as a prognostic marker. Transcriptomic analysis of the genes included in the CNV and associated with prognosis didn\u2019t 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 \u2018quiet\u2019 profile, leaving the mechanism underlying tumorigenesis open to question.",
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"name": "Acta Neuropathologica Communications",
"publisher": "Springer Nature",
"type": "Periodical"
},
{
"issueNumber": "1",
"type": "PublicationIssue"
},
{
"type": "PublicationVolume",
"volumeNumber": "8"
}
],
"keywords": [
"clinico-pathological classification",
"logistic regression models",
"CGH array analysis",
"copy number variations",
"tumor prognosis",
"prognosis marker",
"immunonegative tumours",
"tumor types",
"lactotroph tumors",
"grading classification",
"effects of alterations",
"tumors",
"array analysis",
"regression models",
"prognosis",
"recurrence",
"transcriptomic analysis",
"gonadotrophs",
"corticotrophs",
"somatotrophs",
"PitNETs",
"lactotrophs",
"number variations",
"markers",
"alterations",
"years",
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"model",
"variation",
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],
"name": "Chromosomal instability in the prediction of pituitary neuroendocrine tumors prognosis",
"pagination": "190",
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