Case Report: Genetic Alterations Associated with the Progression of Carotid Paraganglioma
Paragangliomas (PGLs) are rare neuroendocrine tumors that can develop from any paraganglion across the body. The carotid body is the most often location of PGLs in the head and neck region. Carotid PGLs (CPGLs) are characterized by predominantly non-aggressive behavior; however, all tumors have the...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | Current Issues in Molecular Biology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1467-3045/43/3/159 |
| _version_ | 1797505857999601664 |
|---|---|
| author | Vladislav Pavlov Anastasiya Snezhkina Dmitry Kalinin Alexander Golovyuk Anastasiya Kobelyatskaya Ildar Bakhtogarimov Nadezhda Volchenko George Krasnov Anna Kudryavtseva |
| author_facet | Vladislav Pavlov Anastasiya Snezhkina Dmitry Kalinin Alexander Golovyuk Anastasiya Kobelyatskaya Ildar Bakhtogarimov Nadezhda Volchenko George Krasnov Anna Kudryavtseva |
| author_sort | Vladislav Pavlov |
| collection | DOAJ |
| description | Paragangliomas (PGLs) are rare neuroendocrine tumors that can develop from any paraganglion across the body. The carotid body is the most often location of PGLs in the head and neck region. Carotid PGLs (CPGLs) are characterized by predominantly non-aggressive behavior; however, all tumors have the potential to metastasize. To date, molecular mechanisms of paraganglioma progression remain elusive. We report a case of a 38-year-old woman with metastatic CPGL manifesting as a recurrent tumor with lymph node metastasis. The tumor was fast-growing and had a high Ki-67 proliferation index. Immunohistochemical (IHC) examination and whole-exome sequencing were performed for both recurrent tumor and metastasis. A germline pathogenic splice acceptor variant in the <i>SDHB</i> gene was found in the patient. Immunoreactivity of the SDHB subunit was weak diffuse in both samples, indicating deficiency of the succinate dehydrogenase. Moreover, the recurrent tumor exhibited loss of heterozygosity (LOH) at the SDHB locus, that is according to Knudson’s "two-hit" hypothesis of cancer causation. We also identified a rare somatic promotor mutation in the <i>TERT</i> gene associated with the tumor progression. Obtained results confirmed the indicative role of the germline <i>SDHB</i> mutation for metastatic CPGLs, as well as the potential prognostic value of the <i>TERT</i> promoter mutation. |
| first_indexed | 2024-03-10T04:24:20Z |
| format | Article |
| id | doaj.art-e3050f15fe27403d9b56b4ee157f3b2b |
| institution | Directory Open Access Journal |
| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-10T04:24:20Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Issues in Molecular Biology |
| spelling | doaj.art-e3050f15fe27403d9b56b4ee157f3b2b2023-11-23T07:44:31ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452021-12-014332266227510.3390/cimb43030159Case Report: Genetic Alterations Associated with the Progression of Carotid ParagangliomaVladislav Pavlov0Anastasiya Snezhkina1Dmitry Kalinin2Alexander Golovyuk3Anastasiya Kobelyatskaya4Ildar Bakhtogarimov5Nadezhda Volchenko6George Krasnov7Anna Kudryavtseva8Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, RussiaEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, RussiaVishnevsky Institute of Surgery, Ministry of Health of the Russian Federation, 117997 Moscow, RussiaVishnevsky Institute of Surgery, Ministry of Health of the Russian Federation, 117997 Moscow, RussiaEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, RussiaEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, RussiaNational Medical Research Radiological Center, Ministry of Health of the Russian Federation, 125284 Moscow, RussiaEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, RussiaEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, RussiaParagangliomas (PGLs) are rare neuroendocrine tumors that can develop from any paraganglion across the body. The carotid body is the most often location of PGLs in the head and neck region. Carotid PGLs (CPGLs) are characterized by predominantly non-aggressive behavior; however, all tumors have the potential to metastasize. To date, molecular mechanisms of paraganglioma progression remain elusive. We report a case of a 38-year-old woman with metastatic CPGL manifesting as a recurrent tumor with lymph node metastasis. The tumor was fast-growing and had a high Ki-67 proliferation index. Immunohistochemical (IHC) examination and whole-exome sequencing were performed for both recurrent tumor and metastasis. A germline pathogenic splice acceptor variant in the <i>SDHB</i> gene was found in the patient. Immunoreactivity of the SDHB subunit was weak diffuse in both samples, indicating deficiency of the succinate dehydrogenase. Moreover, the recurrent tumor exhibited loss of heterozygosity (LOH) at the SDHB locus, that is according to Knudson’s "two-hit" hypothesis of cancer causation. We also identified a rare somatic promotor mutation in the <i>TERT</i> gene associated with the tumor progression. Obtained results confirmed the indicative role of the germline <i>SDHB</i> mutation for metastatic CPGLs, as well as the potential prognostic value of the <i>TERT</i> promoter mutation.https://www.mdpi.com/1467-3045/43/3/159carotid paragangliomarecurrent tumormetastasis<i>SDHB</i><i>TERT</i>whole-exome sequencing |
| spellingShingle | Vladislav Pavlov Anastasiya Snezhkina Dmitry Kalinin Alexander Golovyuk Anastasiya Kobelyatskaya Ildar Bakhtogarimov Nadezhda Volchenko George Krasnov Anna Kudryavtseva Case Report: Genetic Alterations Associated with the Progression of Carotid Paraganglioma Current Issues in Molecular Biology carotid paraganglioma recurrent tumor metastasis <i>SDHB</i> <i>TERT</i> whole-exome sequencing |
| title | Case Report: Genetic Alterations Associated with the Progression of Carotid Paraganglioma |
| title_full | Case Report: Genetic Alterations Associated with the Progression of Carotid Paraganglioma |
| title_fullStr | Case Report: Genetic Alterations Associated with the Progression of Carotid Paraganglioma |
| title_full_unstemmed | Case Report: Genetic Alterations Associated with the Progression of Carotid Paraganglioma |
| title_short | Case Report: Genetic Alterations Associated with the Progression of Carotid Paraganglioma |
| title_sort | case report genetic alterations associated with the progression of carotid paraganglioma |
| topic | carotid paraganglioma recurrent tumor metastasis <i>SDHB</i> <i>TERT</i> whole-exome sequencing |
| url | https://www.mdpi.com/1467-3045/43/3/159 |
| work_keys_str_mv | AT vladislavpavlov casereportgeneticalterationsassociatedwiththeprogressionofcarotidparaganglioma AT anastasiyasnezhkina casereportgeneticalterationsassociatedwiththeprogressionofcarotidparaganglioma AT dmitrykalinin casereportgeneticalterationsassociatedwiththeprogressionofcarotidparaganglioma AT alexandergolovyuk casereportgeneticalterationsassociatedwiththeprogressionofcarotidparaganglioma AT anastasiyakobelyatskaya casereportgeneticalterationsassociatedwiththeprogressionofcarotidparaganglioma AT ildarbakhtogarimov casereportgeneticalterationsassociatedwiththeprogressionofcarotidparaganglioma AT nadezhdavolchenko casereportgeneticalterationsassociatedwiththeprogressionofcarotidparaganglioma AT georgekrasnov casereportgeneticalterationsassociatedwiththeprogressionofcarotidparaganglioma AT annakudryavtseva casereportgeneticalterationsassociatedwiththeprogressionofcarotidparaganglioma |