Back to Search
Start Over
Large Genomic Aberrations in Corticotropinomas Are Associated With Greater Aggressiveness.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2019 May 01; Vol. 104 (5), pp. 1792-1801. - Publication Year :
- 2019
-
Abstract
- Context: Genomic losses/gains are associated with cancer progression and prognosis. In pituitary adenomas, analyses of copy number variations (CNVs) have shown that a subset of adenomas have higher genomic variability. However, whether CNVs are associated with tumor aggressiveness and prognosis has not been determined.<br />Objective: We hypothesized that somatic CNVs of pituitary tumors may play a role in the progression and aggressiveness of pituitary corticotropinomas in children and adolescents.<br />Samples and Design: Paired germline and tumor DNA samples from 27 pediatric patients with Cushing disease (CD), were subjected to whole exome sequencing. Somatic CNVs were identified using the ExomeDepth tool. Clinical, histological, and biochemical data from the patients were collected and correlated with the results of the CNV analysis.<br />Results: Chromosomal instability, involving 23% to 59% of the tumor genome, was noted in 5 of the 27 samples (18.5%). The patients with tumors showing chromosomal instability had similar clinical and biochemical characteristics to the remaining patients, except for tumor size, which was larger (median size 18 mm vs 5.5 mm, P = 0.005). Tumors with chromosomal instability were also associated with a higher rate of invasion of the cavernous sinus (P = 0.029). There was insufficient information on persistence or recurrence of CD to determine whether the risk was higher in those with chromosomal instability.<br />Conclusions: A subgroup of corticotropinomas demonstrates chromosomal instability that is associated with markers of aggressiveness of these adenomas. It appears that more genomic gains/losses in a few, rare corticotropinomas may predict poorer prognosis for pediatric patients with CD.<br /> (Published by Oxford University Press on behalf of the Endocrine Society 2019.)
- Subjects :
- ACTH-Secreting Pituitary Adenoma genetics
Adolescent
Cushing Syndrome genetics
DNA Copy Number Variations
Female
Follow-Up Studies
Genomic Instability
Humans
Male
Prognosis
ACTH-Secreting Pituitary Adenoma pathology
Biomarkers analysis
Chromosome Aberrations
Cushing Syndrome pathology
Genetic Predisposition to Disease
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7197
- Volume :
- 104
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 30597087
- Full Text :
- https://doi.org/10.1210/jc.2018-02164