Whole Exome Sequencing Uncovers Germline Variants of Cancer-Related Genes in Sporadic Pheochromocytoma
Background. Pheochromocytomas (PCCs) show the highest degree of heritability in human neoplasms. However, despite the wide number of alterations until now reported in PCCs, it is likely that other susceptibility genes remain still unknown, especially for those PCCs not clearly syndromic. Methods. Wh...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-01-01
|
| Series: | International Journal of Genomics |
| Online Access: | http://dx.doi.org/10.1155/2018/6582014 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832552343860674560 |
|---|---|
| author | Milena Urbini Margherita Nannini Annalisa Astolfi Valentina Indio Valentina Vicennati Matilde De Luca Giuseppe Tarantino Federica Corso Maristella Saponara Lidia Gatto Donatella Santini Guido Di Dalmazi Uberto Pagotto Renato Pasquali Andrea Pession Guido Biasco Maria A. Pantaleo |
| author_facet | Milena Urbini Margherita Nannini Annalisa Astolfi Valentina Indio Valentina Vicennati Matilde De Luca Giuseppe Tarantino Federica Corso Maristella Saponara Lidia Gatto Donatella Santini Guido Di Dalmazi Uberto Pagotto Renato Pasquali Andrea Pession Guido Biasco Maria A. Pantaleo |
| author_sort | Milena Urbini |
| collection | DOAJ |
| description | Background. Pheochromocytomas (PCCs) show the highest degree of heritability in human neoplasms. However, despite the wide number of alterations until now reported in PCCs, it is likely that other susceptibility genes remain still unknown, especially for those PCCs not clearly syndromic. Methods. Whole exome sequencing of tumor DNA was performed on a set of twelve PCCs clinically defined as sporadic. Results. About 50% of PCCs examined had somatic mutations on the known susceptibility VHL, NF1, and RET genes. In addition to these driver events, mutations on SYNE1, ABCC10, and RAD54B genes were also detected. Moreover, extremely rare germline variants were present in half of the sporadic PCC samples analyzed, in particular variants of MAX and SAMD9L were detected in the germline of cases wild-type for mutations in the known susceptibility genes. Conclusions. Additional somatic passenger mutations can be associated with known susceptibility VHL, NF1, and RET genes in PCCs, and a wide number of germline variants with still unknown clinical significance can be detected in these patients. Therefore, many efforts should be aimed to better define the pathogenetic role of all these germline variants for discovering novel potential therapeutic targets for this disease still orphan of effective treatments. |
| format | Article |
| id | doaj-art-266029af3d70419fbb97fab551f8a5a1 |
| institution | Kabale University |
| issn | 2314-436X 2314-4378 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Genomics |
| spelling | doaj-art-266029af3d70419fbb97fab551f8a5a12025-02-03T05:58:46ZengWileyInternational Journal of Genomics2314-436X2314-43782018-01-01201810.1155/2018/65820146582014Whole Exome Sequencing Uncovers Germline Variants of Cancer-Related Genes in Sporadic PheochromocytomaMilena Urbini0Margherita Nannini1Annalisa Astolfi2Valentina Indio3Valentina Vicennati4Matilde De Luca5Giuseppe Tarantino6Federica Corso7Maristella Saponara8Lidia Gatto9Donatella Santini10Guido Di Dalmazi11Uberto Pagotto12Renato Pasquali13Andrea Pession14Guido Biasco15Maria A. Pantaleo16“Giorgio Prodi” Cancer Research Center, University of Bologna, Bologna, ItalyDepartment of Specialized, Experimental and Diagnostic Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy“Giorgio Prodi” Cancer Research Center, University of Bologna, Bologna, Italy“Giorgio Prodi” Cancer Research Center, University of Bologna, Bologna, ItalyEndocrinology Unit, Department of Medical and Surgical Sciences, Center for Applied Biomedical Research, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy“Giorgio Prodi” Cancer Research Center, University of Bologna, Bologna, Italy“Giorgio Prodi” Cancer Research Center, University of Bologna, Bologna, ItalyDepartment of Specialized, Experimental and Diagnostic Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, ItalyDepartment of Specialized, Experimental and Diagnostic Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, ItalyDepartment of Specialized, Experimental and Diagnostic Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, ItalyPathology Unit, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, ItalyEndocrinology Unit, Department of Medical and Surgical Sciences, Center for Applied Biomedical Research, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, ItalyEndocrinology Unit, Department of Medical and Surgical Sciences, Center for Applied Biomedical Research, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, ItalyEndocrinology Unit, Department of Medical and Surgical Sciences, Center for Applied Biomedical Research, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, ItalyDepartment of Specialized, Experimental and Diagnostic Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy“Giorgio Prodi” Cancer Research Center, University of Bologna, Bologna, Italy“Giorgio Prodi” Cancer Research Center, University of Bologna, Bologna, ItalyBackground. Pheochromocytomas (PCCs) show the highest degree of heritability in human neoplasms. However, despite the wide number of alterations until now reported in PCCs, it is likely that other susceptibility genes remain still unknown, especially for those PCCs not clearly syndromic. Methods. Whole exome sequencing of tumor DNA was performed on a set of twelve PCCs clinically defined as sporadic. Results. About 50% of PCCs examined had somatic mutations on the known susceptibility VHL, NF1, and RET genes. In addition to these driver events, mutations on SYNE1, ABCC10, and RAD54B genes were also detected. Moreover, extremely rare germline variants were present in half of the sporadic PCC samples analyzed, in particular variants of MAX and SAMD9L were detected in the germline of cases wild-type for mutations in the known susceptibility genes. Conclusions. Additional somatic passenger mutations can be associated with known susceptibility VHL, NF1, and RET genes in PCCs, and a wide number of germline variants with still unknown clinical significance can be detected in these patients. Therefore, many efforts should be aimed to better define the pathogenetic role of all these germline variants for discovering novel potential therapeutic targets for this disease still orphan of effective treatments.http://dx.doi.org/10.1155/2018/6582014 |
| spellingShingle | Milena Urbini Margherita Nannini Annalisa Astolfi Valentina Indio Valentina Vicennati Matilde De Luca Giuseppe Tarantino Federica Corso Maristella Saponara Lidia Gatto Donatella Santini Guido Di Dalmazi Uberto Pagotto Renato Pasquali Andrea Pession Guido Biasco Maria A. Pantaleo Whole Exome Sequencing Uncovers Germline Variants of Cancer-Related Genes in Sporadic Pheochromocytoma International Journal of Genomics |
| title | Whole Exome Sequencing Uncovers Germline Variants of Cancer-Related Genes in Sporadic Pheochromocytoma |
| title_full | Whole Exome Sequencing Uncovers Germline Variants of Cancer-Related Genes in Sporadic Pheochromocytoma |
| title_fullStr | Whole Exome Sequencing Uncovers Germline Variants of Cancer-Related Genes in Sporadic Pheochromocytoma |
| title_full_unstemmed | Whole Exome Sequencing Uncovers Germline Variants of Cancer-Related Genes in Sporadic Pheochromocytoma |
| title_short | Whole Exome Sequencing Uncovers Germline Variants of Cancer-Related Genes in Sporadic Pheochromocytoma |
| title_sort | whole exome sequencing uncovers germline variants of cancer related genes in sporadic pheochromocytoma |
| url | http://dx.doi.org/10.1155/2018/6582014 |
| work_keys_str_mv | AT milenaurbini wholeexomesequencinguncoversgermlinevariantsofcancerrelatedgenesinsporadicpheochromocytoma AT margheritanannini wholeexomesequencinguncoversgermlinevariantsofcancerrelatedgenesinsporadicpheochromocytoma AT annalisaastolfi wholeexomesequencinguncoversgermlinevariantsofcancerrelatedgenesinsporadicpheochromocytoma AT valentinaindio wholeexomesequencinguncoversgermlinevariantsofcancerrelatedgenesinsporadicpheochromocytoma AT valentinavicennati wholeexomesequencinguncoversgermlinevariantsofcancerrelatedgenesinsporadicpheochromocytoma AT matildedeluca wholeexomesequencinguncoversgermlinevariantsofcancerrelatedgenesinsporadicpheochromocytoma AT giuseppetarantino wholeexomesequencinguncoversgermlinevariantsofcancerrelatedgenesinsporadicpheochromocytoma AT federicacorso wholeexomesequencinguncoversgermlinevariantsofcancerrelatedgenesinsporadicpheochromocytoma AT maristellasaponara wholeexomesequencinguncoversgermlinevariantsofcancerrelatedgenesinsporadicpheochromocytoma AT lidiagatto wholeexomesequencinguncoversgermlinevariantsofcancerrelatedgenesinsporadicpheochromocytoma AT donatellasantini wholeexomesequencinguncoversgermlinevariantsofcancerrelatedgenesinsporadicpheochromocytoma AT guidodidalmazi wholeexomesequencinguncoversgermlinevariantsofcancerrelatedgenesinsporadicpheochromocytoma AT ubertopagotto wholeexomesequencinguncoversgermlinevariantsofcancerrelatedgenesinsporadicpheochromocytoma AT renatopasquali wholeexomesequencinguncoversgermlinevariantsofcancerrelatedgenesinsporadicpheochromocytoma AT andreapession wholeexomesequencinguncoversgermlinevariantsofcancerrelatedgenesinsporadicpheochromocytoma AT guidobiasco wholeexomesequencinguncoversgermlinevariantsofcancerrelatedgenesinsporadicpheochromocytoma AT mariaapantaleo wholeexomesequencinguncoversgermlinevariantsofcancerrelatedgenesinsporadicpheochromocytoma |