Novel Germline <i>PHD2</i> Variant in a Metastatic Pheochromocytoma and Chronic Myeloid Leukemia, but in the Absence of Polycythemia
Background: Pheochromocytoma (Pheo) and paraganglioma (PGL) are rare tumors, mostly resulting from pathogenic variants of predisposing genes, with a genetic contribution that now stands at around 70%. Germline variants account for approximately 40%, while the remaining 30% is attributable to somatic...
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| Format: | Article |
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MDPI AG
2022-08-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1648-9144/58/8/1113 |
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| author | Aldesia Provenzano Massimiliano Chetta Giuseppina De Filpo Giulia Cantini Andrea La Barbera Gabriella Nesi Raffaella Santi Serena Martinelli Elena Rapizzi Michaela Luconi Mario Maggi Massimo Mannelli Tonino Ercolino Letizia Canu |
| author_facet | Aldesia Provenzano Massimiliano Chetta Giuseppina De Filpo Giulia Cantini Andrea La Barbera Gabriella Nesi Raffaella Santi Serena Martinelli Elena Rapizzi Michaela Luconi Mario Maggi Massimo Mannelli Tonino Ercolino Letizia Canu |
| author_sort | Aldesia Provenzano |
| collection | DOAJ |
| description | Background: Pheochromocytoma (Pheo) and paraganglioma (PGL) are rare tumors, mostly resulting from pathogenic variants of predisposing genes, with a genetic contribution that now stands at around 70%. Germline variants account for approximately 40%, while the remaining 30% is attributable to somatic variants. Objective: This study aimed to describe a new <i>PHD2</i> (<i>EGLN1</i>) variant in a patient affected by metastatic Pheo and chronic myeloid leukemia (CML) without polycythemia and to emphasize the need to adopt a comprehensive next-generation sequencing (NGS) panel. Methods: Genetic analysis was carried out by NGS. This analysis was initially performed using a panel of genes known for tumor predisposition (<i>EGLN1</i>, <i>EPAS1</i>, <i>FH</i>, <i>KIF1B</i>β, <i>MAX</i>, <i>NF1</i>, <i>RET</i>, <i>SDHA</i>, <i>SDHAF2</i>, <i>SDHB</i>, <i>SDHC</i>, <i>SDHD</i>, <i>TMEM127</i>, and <i>VHL</i>), followed initially by SNP-CGH array, to exclude the presence of the pathogenic Copy Number Variants (CNVs) and the loss of heterozygosity (LOH) and subsequently by whole exome sequencing (WES) comparative sequence analysis of the DNA extracted from tumor fragments and peripheral blood. Results: We found a novel germline <i>PHD2</i> (<i>EGLN1</i>) gene variant, c.153G>A, p.W51*, in a patient affected by metastatic Pheo and chronic myeloid leukemia (CML) in the absence of polycythemia. Conclusions: According to the latest guidelines, it is mandatory to perform genetic analysis in all Pheo/PGL cases regardless of phenotype. In patients with metastatic disease and no evidence of polycythemia, we propose testing for <i>PHD2</i> (<i>EGLN1</i>) gene variants. A possible correlation between <i>PHD2</i> (<i>EGLN1</i>) pathogenic variants and CML clinical course should be considered. |
| first_indexed | 2024-03-09T12:58:31Z |
| format | Article |
| id | doaj.art-1ea3b8f1701e4fdb8982deb96e3a7936 |
| institution | Directory Open Access Journal |
| issn | 1010-660X 1648-9144 |
| language | English |
| last_indexed | 2024-03-09T12:58:31Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
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| series | Medicina |
| spelling | doaj.art-1ea3b8f1701e4fdb8982deb96e3a79362023-11-30T21:56:52ZengMDPI AGMedicina1010-660X1648-91442022-08-01588111310.3390/medicina58081113Novel Germline <i>PHD2</i> Variant in a Metastatic Pheochromocytoma and Chronic Myeloid Leukemia, but in the Absence of PolycythemiaAldesia Provenzano0Massimiliano Chetta1Giuseppina De Filpo2Giulia Cantini3Andrea La Barbera4Gabriella Nesi5Raffaella Santi6Serena Martinelli7Elena Rapizzi8Michaela Luconi9Mario Maggi10Massimo Mannelli11Tonino Ercolino12Letizia Canu13Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, ItalyMedical Genetics, Azienda Ospedaliera di Rilievo Nazionale (A.O.R.N.) Cardarelli, Padiglione, 80131 Naples, ItalyDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, ItalyCentro di Ricerca e Innovazione sulle Patologie Surrenaliche, AOU Careggi, 50139 Florence, ItalyCentro di Ricerca e Innovazione sulle Patologie Surrenaliche, AOU Careggi, 50139 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, ItalyCentro di Ricerca e Innovazione sulle Patologie Surrenaliche, AOU Careggi, 50139 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, ItalyCentro di Ricerca e Innovazione sulle Patologie Surrenaliche, AOU Careggi, 50139 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, ItalyBackground: Pheochromocytoma (Pheo) and paraganglioma (PGL) are rare tumors, mostly resulting from pathogenic variants of predisposing genes, with a genetic contribution that now stands at around 70%. Germline variants account for approximately 40%, while the remaining 30% is attributable to somatic variants. Objective: This study aimed to describe a new <i>PHD2</i> (<i>EGLN1</i>) variant in a patient affected by metastatic Pheo and chronic myeloid leukemia (CML) without polycythemia and to emphasize the need to adopt a comprehensive next-generation sequencing (NGS) panel. Methods: Genetic analysis was carried out by NGS. This analysis was initially performed using a panel of genes known for tumor predisposition (<i>EGLN1</i>, <i>EPAS1</i>, <i>FH</i>, <i>KIF1B</i>β, <i>MAX</i>, <i>NF1</i>, <i>RET</i>, <i>SDHA</i>, <i>SDHAF2</i>, <i>SDHB</i>, <i>SDHC</i>, <i>SDHD</i>, <i>TMEM127</i>, and <i>VHL</i>), followed initially by SNP-CGH array, to exclude the presence of the pathogenic Copy Number Variants (CNVs) and the loss of heterozygosity (LOH) and subsequently by whole exome sequencing (WES) comparative sequence analysis of the DNA extracted from tumor fragments and peripheral blood. Results: We found a novel germline <i>PHD2</i> (<i>EGLN1</i>) gene variant, c.153G>A, p.W51*, in a patient affected by metastatic Pheo and chronic myeloid leukemia (CML) in the absence of polycythemia. Conclusions: According to the latest guidelines, it is mandatory to perform genetic analysis in all Pheo/PGL cases regardless of phenotype. In patients with metastatic disease and no evidence of polycythemia, we propose testing for <i>PHD2</i> (<i>EGLN1</i>) gene variants. A possible correlation between <i>PHD2</i> (<i>EGLN1</i>) pathogenic variants and CML clinical course should be considered.https://www.mdpi.com/1648-9144/58/8/1113germline variants<i>PHD2</i> genemetastatic pheochromocytomaradiometabolic therapyPPRTchronic myeloid leukemia |
| spellingShingle | Aldesia Provenzano Massimiliano Chetta Giuseppina De Filpo Giulia Cantini Andrea La Barbera Gabriella Nesi Raffaella Santi Serena Martinelli Elena Rapizzi Michaela Luconi Mario Maggi Massimo Mannelli Tonino Ercolino Letizia Canu Novel Germline <i>PHD2</i> Variant in a Metastatic Pheochromocytoma and Chronic Myeloid Leukemia, but in the Absence of Polycythemia Medicina germline variants <i>PHD2</i> gene metastatic pheochromocytoma radiometabolic therapy PPRT chronic myeloid leukemia |
| title | Novel Germline <i>PHD2</i> Variant in a Metastatic Pheochromocytoma and Chronic Myeloid Leukemia, but in the Absence of Polycythemia |
| title_full | Novel Germline <i>PHD2</i> Variant in a Metastatic Pheochromocytoma and Chronic Myeloid Leukemia, but in the Absence of Polycythemia |
| title_fullStr | Novel Germline <i>PHD2</i> Variant in a Metastatic Pheochromocytoma and Chronic Myeloid Leukemia, but in the Absence of Polycythemia |
| title_full_unstemmed | Novel Germline <i>PHD2</i> Variant in a Metastatic Pheochromocytoma and Chronic Myeloid Leukemia, but in the Absence of Polycythemia |
| title_short | Novel Germline <i>PHD2</i> Variant in a Metastatic Pheochromocytoma and Chronic Myeloid Leukemia, but in the Absence of Polycythemia |
| title_sort | novel germline i phd2 i variant in a metastatic pheochromocytoma and chronic myeloid leukemia but in the absence of polycythemia |
| topic | germline variants <i>PHD2</i> gene metastatic pheochromocytoma radiometabolic therapy PPRT chronic myeloid leukemia |
| url | https://www.mdpi.com/1648-9144/58/8/1113 |
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