liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Domain landscapes of somatic NF1 mutations in pheochromocytoma and paraganglioma
Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Univ Sfax, Tunisia.
Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0003-4184-5264
Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.ORCID iD: 0000-0002-0054-664X
Show others and affiliations
2023 (English)In: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 872, article id 147432Article in journal (Refereed) Published
Abstract [en]

Pheochromocytoma and paraganglioma (PPGL), are rare neuroendocrine tumors arising from the adrenal me-dulla and extra-adrenal paraganglia, respectively. Up to about 60% are explained by germline or somatic mu-tations in one of the major known susceptibility genes e.g., in NF1, RET, VHL, SDHx, MAX and HRAS. Targeted Next Generation Sequencing was performed in 14 sporadic tumors using a panel including 26 susceptibility genes to characterize the mutation profile. A total of 6 germline and 8 somatic variants were identified. The most frequent somatic mutations were found in NF1 (36%), four have not been reported earlier in PCC or PGL. Gene expression profile analysis showed that NF1 mutated tumors are classified into RTK3 subtype, cluster 2, with a high expression of genes associated with chromaffin cell differentiation, and into a RTK2 subtype, cluster 2, as well with overexpression of genes associated with cortisol biosynthesis. On the other hand, by analyzing the entire probe set on the array and TCGA data, ALDOC was found as the most significantly down regulated gene in NF1-mutated tumors compared to NF1-wild-type. Differential gene expression analysis showed a significant difference between Nt -and Ct-NF1 domains in mutated tumors probably engaging different cellular pathways. Notably, we had a metastatic PCC with a Ct-NF1 frameshift mutation and when performing protein docking analysis, Ct-NF1 showed an interaction with Nt-FAK suggesting their involvement in cell adhesion and cell growth. These results show that depending on the location of the NF1-mutation different pathways are activated in PPGLs. Further studies are required to clarify their clinical significance.

Place, publisher, year, edition, pages
ELSEVIER , 2023. Vol. 872, article id 147432
Keywords [en]
PPGL; NF1; Mutation; NF1-domain; ALDOC; FAK
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:liu:diva-195335DOI: 10.1016/j.gene.2023.147432ISI: 000990895600001PubMedID: 37062455OAI: oai:DiVA.org:liu-195335DiVA, id: diva2:1772184
Note

Funding Agencies|ALF Grant from Region Ostergotland; [RO-532021]

Available from: 2023-06-21 Created: 2023-06-21 Last updated: 2024-05-03

Open Access in DiVA

fulltext(4043 kB)323 downloads
File information
File name FULLTEXT01.pdfFile size 4043 kBChecksum SHA-512
2abcc27ec25ba4ed72aa0858f52c75428fc8798b24addbd485199e99ba6bbd9eb5c5e05d82b153b4f3b2f3a4fc98776473a8018278fd2565c5ebcf72607de4ef
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records

Volpe, Massimiliano

Search in DiVA

By author/editor
Tababi, MounaVolpe, MassimilianoGimm, OliverSöderkvist, Peter
By organisation
Division of Cell BiologyFaculty of Medicine and Health SciencesDivision of Surgery, Orthopedics and OncologyDepartment of Surgery in Linköping
In the same journal
Gene
Medical Genetics

Search outside of DiVA

GoogleGoogle Scholar
Total: 325 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 332 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf