Case Series: ATRX Variants in Four Patients with Metastatic Pheochromocytoma.

Autor:	Cortez BN; Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States., Kuo MJM; Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States., Jha A; Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States., Patel M; Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.; Center for Cancer Research, Laboratory of Pathology, National Cancer Institute, Bethesda, MD, United States., Carrasquillo JA; Molecular Imaging Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States., Prodanov T; Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States., Charles KM; Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States., Talvacchio S; Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States., Derkyi A; Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States., Lin FI; Molecular Imaging Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States., Taïeb D; Department of Nuclear Medicine, La Timone University Hospital & Centre de Recherches en Cancérologie de Marseille (CERIMED) & French Institute of Health and Medical Research (Inserm) UMR1068 Marseille Cancerology Research Center, Institut Paoli-Calmettes, Aix-Marseille University, Marseille, France., Del Rivero J; Developemental Therapeutics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States., Pacak K; Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2024 Sep 16; Vol. 15, pp. 1399847. Date of Electronic Publication: 2024 Sep 16 (Print Publication: 2024).
DOI:	10.3389/fendo.2024.1399847
Abstrakt:	Few reports have highlighted the rare presence of somatic ATRX variants in clinically aggressive, metastatic pheochromocytoma/paraganglioma (PCC/PGL); however, none have addressed detailed clinical presentation (including biochemistry and imaging) and management of these patients. Here, we address these clinical features and management based on four PCC patients with somatic ATRX variants from our National Institutes of Health PCC/PGL cohort. A total of 192 patients underwent exome sequencing (germline, somatic, or both), and four males were found to have somatic ATRX variants (with additional somatic VHL and FH oncogenic variants in patients 2 and 4, respectively). Per-lesion and per-patient comparisons were performed among functional imaging scans performed at the NIH. Biochemical phenotype and response to systemic treatment were evaluated. This mini-series supports prior studies showing aggressive/metastatic PCC in patients with somatic ATRX variants, as all developed widespread metastatic disease. All four PCC patients presented with noradrenergic biochemical phenotype, and some with significant elevation in 3-methoxytyramine. ¹⁸ F-FDOPA PET/CT was found to be the superior functional imaging modality, with 100% lesion detection rate when compared to that of ⁶⁸ Ga-DOTATATE, ¹⁸ F-FDG, ¹⁸ F-FDA, and ¹²³ I-MIBG scans. While patients did not respond to chemotherapy or tyrosine kinase inhibitors, they responded to targeted radiotherapy using high-specific-activity ¹³¹ I-MIBG (Azedra ^® ) or ¹⁷⁷ Lu-DOTATATE (Lutathera ^® ). Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Cortez, Kuo, Jha, Patel, Carrasquillo, Prodanov, Charles, Talvacchio, Derkyi, Lin, Taïeb, Del Rivero and Pacak.)
Databáze:	MEDLINE
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