Journal of endocrinological investigation · 2026
Mutational patterns in a large cohort of parathyroid carcinomas.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Pandya Chetanya, Uzilov Andrew V, Costa-Guda Jessica, Bellizzi Justin, Taik Patricia, Moe Aye S, Strahl Maya, van der Tuin Karin, Stevenson Mark, Cavaco Branca M, Cetani Filomena, Marcocci Claudio, Karhu Auli, Arola Johanna, Schalin-Jäntti Camilla, Morreau Hans, Thakker Rajesh V, Schadt Eric E, Sebra Robert, Li Shuyu D, Chen Rong, Arnold Andrew
Аннотация
PURPOSE: A lack of targeted therapies make parathyroid carcinoma, a diagnostically challenging malignancy, difficult to treat. The rarity of this tumor type necessitates international collaboration to collect a sizable sample set for study. Prior studies have revealed the importance of driver mutations in the CDC73 gene and identified several putative drivers/aberrant pathways including PI3K/mTOR activation and CCND1 (cyclin D1) amplification. In this study, we sought to better understand the prevalence of putative oncogenic drivers in parathyroid carcinoma.
METHODS: We subjected an expanded cohort of 71 sporadic parathyroid carcinomas, fulfilling stringent WHO criteria, to next-generation DNA sequencing on a custom 16-gene targeted panel.
RESULTS: One or more variant was detected in 44 tumors (62%) and 27 (38%) had no detectable variant. Consistent with earlier studies, we detected loss-of-function CDC73 mutations in 44% (31/70) of evaluable patients, including germline pathogenic variants in 9 patients (36 patients evaluable for somatic status as matched normal available). Notably, mutations in the PI3K/AKT/mTOR pathway were seen in 12.9% (9/70) of evaluable patients, providing further evidence of this as a key therapeutically actionable pathway in parathyroid carcinoma. Correlating genomic and clinical features revealed that patients harboring CDC73 mutations are more likely suffer from life threatening recurrent/metastatic parathyroid carcinoma (P = 0.024) than those without CDC73 variants.
CONCLUSIONS: This genomic characterization of a large parathyroid carcinoma cohort improves understanding of the genomic underpinnings of this rare malignancy, provides novel evidence for genotype-phenotype correlation with recurrent/metastatic disease, and may help to provide a rational basis for individualized treatments.
METHODS: We subjected an expanded cohort of 71 sporadic parathyroid carcinomas, fulfilling stringent WHO criteria, to next-generation DNA sequencing on a custom 16-gene targeted panel.
RESULTS: One or more variant was detected in 44 tumors (62%) and 27 (38%) had no detectable variant. Consistent with earlier studies, we detected loss-of-function CDC73 mutations in 44% (31/70) of evaluable patients, including germline pathogenic variants in 9 patients (36 patients evaluable for somatic status as matched normal available). Notably, mutations in the PI3K/AKT/mTOR pathway were seen in 12.9% (9/70) of evaluable patients, providing further evidence of this as a key therapeutically actionable pathway in parathyroid carcinoma. Correlating genomic and clinical features revealed that patients harboring CDC73 mutations are more likely suffer from life threatening recurrent/metastatic parathyroid carcinoma (P = 0.024) than those without CDC73 variants.
CONCLUSIONS: This genomic characterization of a large parathyroid carcinoma cohort improves understanding of the genomic underpinnings of this rare malignancy, provides novel evidence for genotype-phenotype correlation with recurrent/metastatic disease, and may help to provide a rational basis for individualized treatments.