Genome Near-Haploidization in CDC73-Wildtype Parathyroid Tumors

Recurring parathyroid carcinoma (PC) is foremost associated with germline or somatic CDC73 mutations. We reported three PCs without CDC73 mutations, with massive chromosomal losses, genome near-haploidization with or without endoreduplication/genome doubling. These are characteristic features seen in rare tumor types like oncocytic thyroid carcinoma. We investigated whether similar genomic alterations occur in other parathyroid tumors. We selectively analyzed fourteen parathyroid adenomas (PA, thirteen oncocytic), three atypical parathyroid tumors (APTs, one oncocytic), and one PC, the latter four all negative for CDC73 mutations. Histopathological diagnoses were reviewed according to the WHO classification 2022. All tumors underwent genome-wide SNP array testing with analysis of chromosomal copy number variations (CNVs), imbalances/loss of heterozygosity (LOH). The APTs and PC underwent somatic mutation analysis. Oncocytic PAs exhibited relatively stable genomes with no or minimal chromosomal alterations. Patients with chromosomally altered PA had significantly higher pre-operative serum calcium levels. In contrast, we identified two APTs and one other PC with massive chromosomal losses and genome near-haploidization. Our findings expand the spectrum of chromosomal near-haploidization in APTs and PCs lacking CDC73 mutations.