Background
Whole-exome sequencing studies have not established definitive somatic mutation patterns
among patients with sporadic hyperparathyroidism (HPT). No sequencing has evaluated
multiple endocrine neoplasia type 1 (MEN1)-related HPT. We sought to perform whole-exome
sequencing in HPT patients to identify somatic mutations and associated biological
pathways and tumorigenic networks.
Methods
Whole-exome sequencing was performed on blood and tissue from HPT patients (MEN1 and
sporadic) and somatic single nucleotide variants (SNVs) were identified. Stop-gain
and stop-loss SNVs were analyzed with Ingenuity Pathways Analysis (IPA). Loss of heterozygosity
(LOH) was also assessed.
Results
Sequencing was performed on 4 MEN1 and 10 sporadic cases. Eighteen stop-gain/stop-loss
SNV mutations were identified in 3 MEN1 patients. One complex network was identified
on IPA: Cellular function and maintenance, tumor morphology, and cardiovascular disease
(IPA score = 49). A nonsynonymous SNV of TP53 (lysine-to-glutamic acid change at codon
81) identified in a MEN1 patient was suggested to be a driver mutation (Cancer-specific
High-throughput Annotation of Somatic Mutations; P = .002). All MEN1 and 3/10 sporadic specimens demonstrated LOH of chromosome 11.
Conclusion
Whole-exome sequencing revealed somatic mutations in MEN1 associated with a single
tumorigenic network, whereas sporadic pathogenesis seemed to be more diverse. A somatic
TP53 mutation was also identified. LOH of chromosome 11 was seen in all MEN1 and 3
of 10 sporadic patients.
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Article info
Publication history
Accepted:
August 21,
2014
Footnotes
Financial support for Minerva Romero Arenas was provided in part by the Cornelius and Celia Dupre Fellowship in Surgical Endocrinology.
Identification
Copyright
© 2014 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
