Frequent low-level mutations of Protein Kinase D2 in angiolipoma
(2017) In Journal of Pathology 241(5). p.578-582- Abstract
Tumours displaying differentiation towards normal fat constitute the most common subgroup of soft tissue neoplasms. A series of such tumours was investigated by whole-exome sequencing followed by targeted ultra-deep sequencing. Eighty percent of angiolipomas, but not any other tumour type, displayed mutations in the protein kinase D2 (PRKD2) gene, typically in the part encoding the catalytic domain. The absence of other aberrations at the chromosome or RNA level suggests that PRKD2 mutations are critical for angiolipoma development. Consistently, the mutated PRKD2 alleles were present at low (3-15%) frequencies, indicating that only a subset of the tumour cells is affected. Indeed, by sequencing mature fat cells and other cells... (More)
Tumours displaying differentiation towards normal fat constitute the most common subgroup of soft tissue neoplasms. A series of such tumours was investigated by whole-exome sequencing followed by targeted ultra-deep sequencing. Eighty percent of angiolipomas, but not any other tumour type, displayed mutations in the protein kinase D2 (PRKD2) gene, typically in the part encoding the catalytic domain. The absence of other aberrations at the chromosome or RNA level suggests that PRKD2 mutations are critical for angiolipoma development. Consistently, the mutated PRKD2 alleles were present at low (3-15%) frequencies, indicating that only a subset of the tumour cells is affected. Indeed, by sequencing mature fat cells and other cells separately, the former typically showed the highest mutation frequencies. Thus, we hypothesize that altered PRKD2 signalling in the adipocytic cells drive tumourigenesis and, in agreement with its pivotal role in angiogenesis, induces the vessel formation that is characteristic for angiolipoma.
(Less)
- author
- organization
-
- EXODIAB: Excellence of Diabetes Research in Sweden
- Division of Clinical Genetics
- The genetics of soft tissue tumors (research group)
- Glucose Transport and Protein Trafficking (research group)
- Medical Structural Biology (research group)
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Orthopaedics (Lund)
- Orthopaedic Sarcoma Research (research group)
- Tumor microenvironment
- publishing date
- 2017-01-31
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Pathology
- volume
- 241
- issue
- 5
- pages
- 578 - 582
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:28139834
- scopus:85013804683
- wos:000397466300002
- ISSN
- 0022-3417
- DOI
- 10.1002/path.4865
- language
- English
- LU publication?
- yes
- id
- 07c0c199-e795-407b-bc47-aeb09febec3c
- date added to LUP
- 2017-02-20 12:34:42
- date last changed
- 2025-01-07 07:45:25
@article{07c0c199-e795-407b-bc47-aeb09febec3c, abstract = {{<p>Tumours displaying differentiation towards normal fat constitute the most common subgroup of soft tissue neoplasms. A series of such tumours was investigated by whole-exome sequencing followed by targeted ultra-deep sequencing. Eighty percent of angiolipomas, but not any other tumour type, displayed mutations in the protein kinase D2 (PRKD2) gene, typically in the part encoding the catalytic domain. The absence of other aberrations at the chromosome or RNA level suggests that PRKD2 mutations are critical for angiolipoma development. Consistently, the mutated PRKD2 alleles were present at low (3-15%) frequencies, indicating that only a subset of the tumour cells is affected. Indeed, by sequencing mature fat cells and other cells separately, the former typically showed the highest mutation frequencies. Thus, we hypothesize that altered PRKD2 signalling in the adipocytic cells drive tumourigenesis and, in agreement with its pivotal role in angiogenesis, induces the vessel formation that is characteristic for angiolipoma.</p>}}, author = {{Hofvander, Jakob and Arbajian, Elsa and G Stenkula, Karin and Lindkvist-Petersson, Karin and Larsson, Malin and Nilsson, Jenny and Magnusson, Linda and von Steyern, Fredrik Vult and Rissler, Pehr and L Hornick, Jason and Mertens, Fredrik}}, issn = {{0022-3417}}, language = {{eng}}, month = {{01}}, number = {{5}}, pages = {{578--582}}, publisher = {{John Wiley & Sons Inc.}}, series = {{Journal of Pathology}}, title = {{Frequent low-level mutations of Protein Kinase D2 in angiolipoma}}, url = {{http://dx.doi.org/10.1002/path.4865}}, doi = {{10.1002/path.4865}}, volume = {{241}}, year = {{2017}}, }