-
Je něco špatně v tomto záznamu ?
Head and neck paraganglioma in Pacak-Zhuang syndrome
JS. Rosenblum, Y. Cole, D. Dang, PP. Lookian, H. Alkaissi, M. Patel, AJ. Cappadona, A. Jha, N. Edwards, DR. Donahue, J. Munasinghe, H. Wang, RH. Knutsen, AS. Pappo, RM. Lechan, BA. Kozel, JG. Smirniotopoulos, HJ. Kim, A. Vortmeyer, M. Miettinen,...
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články
Grantová podpora
Eunice Kennedy Shriver National Institute of Child Health and Human Development
NCI NIH HHS - United States
NLK
Directory of Open Access Journals
od 2017
PubMed Central
od 2017
Europe PubMed Central
od 2017
Oxford Journals Open Access Collection
od 2017
ROAD: Directory of Open Access Scholarly Resources
od 2017
PubMed
39821441
DOI
10.1093/jncics/pkaf001
Knihovny.cz E-zdroje
- MeSH
- dospělí MeSH
- hyperplazie MeSH
- karotická tělíska * patologie diagnostické zobrazování MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- mladý dospělý MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- nádory hlavy a krku * genetika patologie diagnostické zobrazování MeSH
- paragangliom * genetika diagnostické zobrazování patologie MeSH
- počítačová rentgenová tomografie MeSH
- pozitronová emisní tomografie MeSH
- transkripční faktory bHLH * genetika analýza MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Head and neck paragangliomas (HNPGLs) are typically slow-growing, hormonally inactive tumors of parasympathetic paraganglia. Inactivation of prolyl-hydroxylase domain-containing 2 protein causing indirect gain-of-function of hypoxia-inducible factor-2α (HIF-2α), encoded by EPAS1, was recently shown to cause carotid body hyperplasia. We previously described a syndrome with multiple sympathetic paragangliomas caused by direct gain-of-function variants in EPAS1 (Pacak-Zhuang syndrome, PZS) and developed a corresponding mouse model. METHODS: We evaluated a cohort of patients with PZS (n = 9) for HNPGL by positron emission tomography, magnetic resonance imaging, and computed tomography and measured carotid body size compared to literature reference values. Resected tumors were evaluated by histologic sectioning and staining. We evaluated the corresponding mouse model at multiple developmental stages (P8 and adult) for lesions of the head and neck by high resolution ex vivo imaging and performed immunohistochemical staining on histologic sections of the identified lesions. RESULTS: hree patients had imaging consistent with HNPGL, one of which warranted resection and was confirmed on histology. Three additional patients had carotid body enlargement (Z-score > 2.0), and 3 had carotid artery malformations. We found that 9 of 10 adult variant mice had carotid body tumors and 6 of 8 had a paraganglioma on the cranio-caval vein, the murine homologue of the superior vena cava; these were also found in 4 of 5 variant mice at post-natal day 8. These tumors and the one resected from a patient were positive for tyrosine hydroxylase, synaptophysin, and chromogranin A. Brown fat in a resected patient tumor carried the EPAS1 pathogenic variant. CONCLUSIONS: These findings (1) suggest HNPGL as a feature of PZS and (2) show that these pathogenic variants are sufficient to cause the development of these tumors, which we believe represents a continuous spectrum of disease starting from hyperplasia.
Center for Adrenal Endocrine Tumors AKESO Prague 5 Czech Republic
Department of Otolaryngology Georgetown University School of Medicine Washington DC United States
Department of Radiology George Washington University Washington DC United States
Division of Endocrinology Diabetes and Metabolism Tufts Medical Center Boston MA United States
Division of Solid Tumor St Jude Children's Research Hospital Memphis TN United States
General Surgical Pathology Section National Institutes of Health Bethesda MD United States
MedPix® National Library of Medicine Bethesda MD United States
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc25010336
- 003
- CZ-PrNML
- 005
- 20250429135502.0
- 007
- ta
- 008
- 250415s2025 enk f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1093/jncics/pkaf001 $2 doi
- 035 __
- $a (PubMed)39821441
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a enk
- 100 1_
- $a Rosenblum, Jared S $u Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States $1 https://orcid.org/0000000159419082
- 245 10
- $a Head and neck paraganglioma in Pacak-Zhuang syndrome / $c JS. Rosenblum, Y. Cole, D. Dang, PP. Lookian, H. Alkaissi, M. Patel, AJ. Cappadona, A. Jha, N. Edwards, DR. Donahue, J. Munasinghe, H. Wang, RH. Knutsen, AS. Pappo, RM. Lechan, BA. Kozel, JG. Smirniotopoulos, HJ. Kim, A. Vortmeyer, M. Miettinen, JD. Heiss, Z. Zhuang, K. Pacak
- 520 9_
- $a BACKGROUND: Head and neck paragangliomas (HNPGLs) are typically slow-growing, hormonally inactive tumors of parasympathetic paraganglia. Inactivation of prolyl-hydroxylase domain-containing 2 protein causing indirect gain-of-function of hypoxia-inducible factor-2α (HIF-2α), encoded by EPAS1, was recently shown to cause carotid body hyperplasia. We previously described a syndrome with multiple sympathetic paragangliomas caused by direct gain-of-function variants in EPAS1 (Pacak-Zhuang syndrome, PZS) and developed a corresponding mouse model. METHODS: We evaluated a cohort of patients with PZS (n = 9) for HNPGL by positron emission tomography, magnetic resonance imaging, and computed tomography and measured carotid body size compared to literature reference values. Resected tumors were evaluated by histologic sectioning and staining. We evaluated the corresponding mouse model at multiple developmental stages (P8 and adult) for lesions of the head and neck by high resolution ex vivo imaging and performed immunohistochemical staining on histologic sections of the identified lesions. RESULTS: hree patients had imaging consistent with HNPGL, one of which warranted resection and was confirmed on histology. Three additional patients had carotid body enlargement (Z-score > 2.0), and 3 had carotid artery malformations. We found that 9 of 10 adult variant mice had carotid body tumors and 6 of 8 had a paraganglioma on the cranio-caval vein, the murine homologue of the superior vena cava; these were also found in 4 of 5 variant mice at post-natal day 8. These tumors and the one resected from a patient were positive for tyrosine hydroxylase, synaptophysin, and chromogranin A. Brown fat in a resected patient tumor carried the EPAS1 pathogenic variant. CONCLUSIONS: These findings (1) suggest HNPGL as a feature of PZS and (2) show that these pathogenic variants are sufficient to cause the development of these tumors, which we believe represents a continuous spectrum of disease starting from hyperplasia.
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a zvířata $7 D000818
- 650 12
- $a nádory hlavy a krku $x genetika $x patologie $x diagnostické zobrazování $7 D006258
- 650 12
- $a transkripční faktory bHLH $x genetika $x analýza $7 D051792
- 650 _2
- $a myši $7 D051379
- 650 _2
- $a ženské pohlaví $7 D005260
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 _2
- $a dospělí $7 D000328
- 650 _2
- $a lidé středního věku $7 D008875
- 650 12
- $a magnetická rezonanční tomografie $7 D008279
- 650 12
- $a paragangliom $x genetika $x diagnostické zobrazování $x patologie $7 D010235
- 650 12
- $a karotická tělíska $x patologie $x diagnostické zobrazování $7 D002344
- 650 _2
- $a modely nemocí na zvířatech $7 D004195
- 650 _2
- $a počítačová rentgenová tomografie $7 D014057
- 650 _2
- $a hyperplazie $7 D006965
- 650 _2
- $a pozitronová emisní tomografie $7 D049268
- 650 _2
- $a mladý dospělý $7 D055815
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Cole, Yasemin $u Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States $1 https://orcid.org/0000000294925885
- 700 1_
- $a Dang, Danielle $u Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States $1 https://orcid.org/0000000250041033
- 700 1_
- $a Lookian, Pashayar P $u Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States $1 https://orcid.org/0000000224369254
- 700 1_
- $a Alkaissi, Hussam $u National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States $1 https://orcid.org/0000000208619348
- 700 1_
- $a Patel, Mayank $u Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States $u General Surgical Pathology Section, National Institutes of Health, Bethesda, MD, United States $1 https://orcid.org/0000000231483717
- 700 1_
- $a Cappadona, Anthony J $u Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States $1 https://orcid.org/0000000259380568
- 700 1_
- $a Jha, Abhishek $u Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States $1 https://orcid.org/0000000214892471
- 700 1_
- $a Edwards, Nancy $u Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States $1 https://orcid.org/0000000156893328
- 700 1_
- $a Donahue, Danielle R $u Mouse Imaging Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States $1 https://orcid.org/000000023371665X
- 700 1_
- $a Munasinghe, Jeeva $u Mouse Imaging Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States $1 https://orcid.org/0000000252955437
- 700 1_
- $a Wang, Herui $u Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States $1 https://orcid.org/0000000322934819
- 700 1_
- $a Knutsen, Russell H $u Laboratory of Vascular and Matrix Genetics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, United States $1 https://orcid.org/0000000167616502
- 700 1_
- $a Pappo, Alberto S $u Division of Solid Tumor, St Jude Children's Research Hospital, Memphis, TN, United States $1 https://orcid.org/0000000253383979 $7 uk2006353711
- 700 1_
- $a Lechan, Ronald M $u Division of Endocrinology, Diabetes & Metabolism, Tufts Medical Center, Boston, MA, United States $1 https://orcid.org/0000000304042323
- 700 1_
- $a Kozel, Beth A $u Laboratory of Vascular and Matrix Genetics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, United States $1 https://orcid.org/0000000297577118
- 700 1_
- $a Smirniotopoulos, James G $u Department of Radiology, George Washington University, Washington, DC, United States $u MedPix® National Library of Medicine, Bethesda, MD, United States $1 https://orcid.org/0000000184227525
- 700 1_
- $a Kim, H Jeffrey $u Department of Otolaryngology, Georgetown University School of Medicine, Washington, DC, United States $u Office of Clinical Director, National Institute on Deafness and Other Communication Disorders, Bethesda, MD, United States
- 700 1_
- $a Vortmeyer, Alexander $u Clinical Pathology & Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, United States $1 https://orcid.org/0000000154375092
- 700 1_
- $a Miettinen, Markku $u General Surgical Pathology Section, National Institutes of Health, Bethesda, MD, United States $1 https://orcid.org/0000000232828107 $7 xx0046080
- 700 1_
- $a Heiss, John D $u Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States $1 https://orcid.org/0000000238900165
- 700 1_
- $a Zhuang, Zhengping $u Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States $1 https://orcid.org/0000000200097370
- 700 1_
- $a Pacak, Karel $u Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States $u Center for Adrenal Endocrine Tumors, AKESO, Prague 5, Czech Republic $1 https://orcid.org/0000000235413767 $7 jo20000074102
- 773 0_
- $w MED00200592 $t JNCI cancer spectrum $x 2515-5091 $g Roč. 9, č. 1 (2025)
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/39821441 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y - $z 0
- 990 __
- $a 20250415 $b ABA008
- 991 __
- $a 20250429135457 $b ABA008
- 999 __
- $a ok $b bmc $g 2311597 $s 1247417
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2025 $b 9 $c 1 $e 20250103 $i 2515-5091 $m JNCI cancer spectrum $n JNCI Cancer Spectr $x MED00200592
- GRA __
- $p Eunice Kennedy Shriver National Institute of Child Health and Human Development
- GRA __
- $p NCI NIH HHS $2 United States
- LZP __
- $a Pubmed-20250415
