Optimizing Genetic Workup in Pheochromocytoma and Paraganglioma by Integrating Diagnostic and Research Approaches
Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors with a strong hereditary background and a large genetic heterogeneity. Identification of the underlying genetic cause is crucial for the management of patients and their families as it aids differentiation between hereditary...
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| Veröffentlicht in: | Cancers 2019-06, Vol.11 (6), p.809 |
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| creator | Gieldon, Laura William, Doreen Hackmann, Karl Jahn, Winnie Jahn, Arne Wagner, Johannes Rump, Andreas Bechmann, Nicole Nölting, Svenja Knösel, Thomas Gudziol, Volker Constantinescu, Georgiana Masjkur, Jimmy Beuschlein, Felix Timmers, Henri Jlm Canu, Letizia Pacak, Karel Robledo, Mercedes Aust, Daniela Schröck, Evelin Eisenhofer, Graeme Richter, Susan Klink, Barbara |
| description | Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors with a strong hereditary background and a large genetic heterogeneity. Identification of the underlying genetic cause is crucial for the management of patients and their families as it aids differentiation between hereditary and sporadic cases. To improve diagnostics and clinical management we tailored an enrichment based comprehensive multi-gene next generation sequencing panel applicable to both analyses of tumor tissue and blood samples. We applied this panel to tumor samples and compared its performance to our current routine diagnostic approach. Routine diagnostic sequencing of 11 PPGL susceptibility genes was applied to blood samples of 65 unselected PPGL patients at a single center in Dresden, Germany. Predisposing germline mutations were identified in 19 (29.2%) patients. Analyses of 28 PPGL tumor tissues using the dedicated PPGL panel revealed pathogenic or likely pathogenic variants in known PPGL susceptibility genes in 21 (75%) cases, including mutations in
and
. These mutations suggest sporadic tumor development. Our results imply a diagnostic benefit from extended molecular tumor testing of PPGLs and consequent improvement of patient management. The approach is promising for determination of prognostic biomarkers that support therapeutic decision-making. |
| doi_str_mv | 10.3390/cancers11060809 |
| format | Article |
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and
. These mutations suggest sporadic tumor development. Our results imply a diagnostic benefit from extended molecular tumor testing of PPGLs and consequent improvement of patient management. The approach is promising for determination of prognostic biomarkers that support therapeutic decision-making.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers11060809</identifier><identifier>PMID: 31212687</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Age ; Breast cancer ; Decision making ; Genes ; Genetic disorders ; Genetics ; Genomics ; Hospitals ; Internal medicine ; Management ; Medical research ; Mutation ; Neuroendocrine tumors ; Next-generation sequencing ; Otolaryngology ; Ovarian cancer ; Paraganglioma ; Pathology ; Patients ; Pheochromocytoma ; Tumors</subject><ispartof>Cancers, 2019-06, Vol.11 (6), p.809</ispartof><rights>2019. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3369-f1e2b049c2d3fa55e8e20f9835218e633005998d8ea59946d548c28354d2cfe23</citedby><cites>FETCH-LOGICAL-c3369-f1e2b049c2d3fa55e8e20f9835218e633005998d8ea59946d548c28354d2cfe23</cites><orcidid>0000-0002-8753-8238 ; 0000-0003-1045-1908 ; 0000-0003-4995-8108 ; 0000-0002-3549-2477 ; 0000-0002-6932-333X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627084/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627084/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,886,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31212687$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gieldon, Laura</creatorcontrib><creatorcontrib>William, Doreen</creatorcontrib><creatorcontrib>Hackmann, Karl</creatorcontrib><creatorcontrib>Jahn, Winnie</creatorcontrib><creatorcontrib>Jahn, Arne</creatorcontrib><creatorcontrib>Wagner, Johannes</creatorcontrib><creatorcontrib>Rump, Andreas</creatorcontrib><creatorcontrib>Bechmann, Nicole</creatorcontrib><creatorcontrib>Nölting, Svenja</creatorcontrib><creatorcontrib>Knösel, Thomas</creatorcontrib><creatorcontrib>Gudziol, Volker</creatorcontrib><creatorcontrib>Constantinescu, Georgiana</creatorcontrib><creatorcontrib>Masjkur, Jimmy</creatorcontrib><creatorcontrib>Beuschlein, Felix</creatorcontrib><creatorcontrib>Timmers, Henri Jlm</creatorcontrib><creatorcontrib>Canu, Letizia</creatorcontrib><creatorcontrib>Pacak, Karel</creatorcontrib><creatorcontrib>Robledo, Mercedes</creatorcontrib><creatorcontrib>Aust, Daniela</creatorcontrib><creatorcontrib>Schröck, Evelin</creatorcontrib><creatorcontrib>Eisenhofer, Graeme</creatorcontrib><creatorcontrib>Richter, Susan</creatorcontrib><creatorcontrib>Klink, Barbara</creatorcontrib><title>Optimizing Genetic Workup in Pheochromocytoma and Paraganglioma by Integrating Diagnostic and Research Approaches</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors with a strong hereditary background and a large genetic heterogeneity. Identification of the underlying genetic cause is crucial for the management of patients and their families as it aids differentiation between hereditary and sporadic cases. To improve diagnostics and clinical management we tailored an enrichment based comprehensive multi-gene next generation sequencing panel applicable to both analyses of tumor tissue and blood samples. We applied this panel to tumor samples and compared its performance to our current routine diagnostic approach. Routine diagnostic sequencing of 11 PPGL susceptibility genes was applied to blood samples of 65 unselected PPGL patients at a single center in Dresden, Germany. Predisposing germline mutations were identified in 19 (29.2%) patients. Analyses of 28 PPGL tumor tissues using the dedicated PPGL panel revealed pathogenic or likely pathogenic variants in known PPGL susceptibility genes in 21 (75%) cases, including mutations in
and
. These mutations suggest sporadic tumor development. Our results imply a diagnostic benefit from extended molecular tumor testing of PPGLs and consequent improvement of patient management. The approach is promising for determination of prognostic biomarkers that support therapeutic decision-making.</description><subject>Age</subject><subject>Breast cancer</subject><subject>Decision making</subject><subject>Genes</subject><subject>Genetic disorders</subject><subject>Genetics</subject><subject>Genomics</subject><subject>Hospitals</subject><subject>Internal medicine</subject><subject>Management</subject><subject>Medical research</subject><subject>Mutation</subject><subject>Neuroendocrine tumors</subject><subject>Next-generation sequencing</subject><subject>Otolaryngology</subject><subject>Ovarian cancer</subject><subject>Paraganglioma</subject><subject>Pathology</subject><subject>Patients</subject><subject>Pheochromocytoma</subject><subject>Tumors</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkd9L3TAUx8OYTHE-700Ke9nLnfnVNHkZiDonXFBE2WPITU_baJvUpBXu_vql6MTdvJyQ88mHc_gi9IXg74wpfGKNtxATIVhgidUHdEBxRVdCKP7x3X0fHaX0gPNhjFSi-oT2GaGEClkdoKfrcXKD--N8W1yCh8nZ4neIj_NYOF_cdBBsF8MQ7HYKgymMr4sbE01rfNu75WWzLa78BG000-I4d6b1IS2ahb2FBCbarjgdxxiM7SB9RnuN6RMcvdZDdP_z4u7s12p9fXl1drpeWcaEWjUE6AZzZWnNGlOWIIHiRklWUiJBMIZxqZSsJZhcuahLLi3NbV5T2wBlh-jHi3ecNwPUFvwUTa_H6AYTtzoYp__veNfpNjxrIWiFJc-Cb6-CGJ5mSJMeXLLQ98ZDmJOmlDOuhGQyo1930IcwR5_Xy1RGuMScZOrkhbIxpBSheRuGYL0kqncSzT-O3-_wxv_Lj_0FLqqe6Q</recordid><startdate>20190611</startdate><enddate>20190611</enddate><creator>Gieldon, 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Felix</au><au>Timmers, Henri Jlm</au><au>Canu, Letizia</au><au>Pacak, Karel</au><au>Robledo, Mercedes</au><au>Aust, Daniela</au><au>Schröck, Evelin</au><au>Eisenhofer, Graeme</au><au>Richter, Susan</au><au>Klink, Barbara</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Optimizing Genetic Workup in Pheochromocytoma and Paraganglioma by Integrating Diagnostic and Research Approaches</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2019-06-11</date><risdate>2019</risdate><volume>11</volume><issue>6</issue><spage>809</spage><pages>809-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors with a strong hereditary background and a large genetic heterogeneity. Identification of the underlying genetic cause is crucial for the management of patients and their families as it aids differentiation between hereditary and sporadic cases. To improve diagnostics and clinical management we tailored an enrichment based comprehensive multi-gene next generation sequencing panel applicable to both analyses of tumor tissue and blood samples. We applied this panel to tumor samples and compared its performance to our current routine diagnostic approach. Routine diagnostic sequencing of 11 PPGL susceptibility genes was applied to blood samples of 65 unselected PPGL patients at a single center in Dresden, Germany. Predisposing germline mutations were identified in 19 (29.2%) patients. Analyses of 28 PPGL tumor tissues using the dedicated PPGL panel revealed pathogenic or likely pathogenic variants in known PPGL susceptibility genes in 21 (75%) cases, including mutations in
and
. These mutations suggest sporadic tumor development. Our results imply a diagnostic benefit from extended molecular tumor testing of PPGLs and consequent improvement of patient management. The approach is promising for determination of prognostic biomarkers that support therapeutic decision-making.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>31212687</pmid><doi>10.3390/cancers11060809</doi><orcidid>https://orcid.org/0000-0002-8753-8238</orcidid><orcidid>https://orcid.org/0000-0003-1045-1908</orcidid><orcidid>https://orcid.org/0000-0003-4995-8108</orcidid><orcidid>https://orcid.org/0000-0002-3549-2477</orcidid><orcidid>https://orcid.org/0000-0002-6932-333X</orcidid><oa>free_for_read</oa></addata></record> |
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| source | PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Age Breast cancer Decision making Genes Genetic disorders Genetics Genomics Hospitals Internal medicine Management Medical research Mutation Neuroendocrine tumors Next-generation sequencing Otolaryngology Ovarian cancer Paraganglioma Pathology Patients Pheochromocytoma Tumors |
| title | Optimizing Genetic Workup in Pheochromocytoma and Paraganglioma by Integrating Diagnostic and Research Approaches |
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