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Frequent low-level mutations of Protein Kinase D2 in angiolipoma

Hofvander, Jakob LU ; Arbajian, Elsa LU ; G Stenkula, Karin LU ; Lindkvist-Petersson, Karin LU ; Larsson, Malin; Nilsson, Jenny LU ; Magnusson, Linda LU ; von Steyern, Fredrik Vult LU ; Rissler, Pehr LU and L Hornick, Jason, et al. (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.

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Please use this url to cite or link to this publication:
@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},
  series       = {Journal of Pathology},
  title        = {Frequent low-level mutations of Protein Kinase D2 in angiolipoma},
  url          = {http://dx.doi.org/10.1002/path.4865},
  volume       = {241},
  year         = {2017},
}