Advanced

Genomic and transcriptomic features of dermatofibrosarcoma protuberans : Unusual chromosomal origin of the COL1A1-PDGFB fusion gene and synergistic effects of amplified regions in tumor development

Köster, Jan LU ; Arbajian, Elsa LU ; Viklund, Björn ; Isaksson, Anders LU ; Hofvander, Jakob LU ; Haglund, Felix ; Bauer, Henrik ; Magnusson, Linda LU ; Mandahl, Nils LU and Mertens, Fredrik LU (2020) In Cancer Genetics 241. p.34-41
Abstract

The dermatofibrosarcoma protuberans family of tumors (DPFT) comprises cutaneous soft tissue neoplasms associated with aberrant PDGFBR signaling, typically through a COL1A1-PDGFB fusion. The aim of the present study was to obtain a better understanding of the chromosomal origin of this fusion and to assess the spectrum of secondary mutations at the chromosome and nucleotide levels. We thus investigated 42 tumor samples from 35 patients using chromosome banding, fluorescence in situ hybridization, single nucleotide polymorphism arrays, and/or massively parallel sequencing (gene panel, whole exome and transcriptome sequencing) methods. We confirmed the age-associated differences in the origin of the COL1A1-PDGFB fusion and could show that... (More)

The dermatofibrosarcoma protuberans family of tumors (DPFT) comprises cutaneous soft tissue neoplasms associated with aberrant PDGFBR signaling, typically through a COL1A1-PDGFB fusion. The aim of the present study was to obtain a better understanding of the chromosomal origin of this fusion and to assess the spectrum of secondary mutations at the chromosome and nucleotide levels. We thus investigated 42 tumor samples from 35 patients using chromosome banding, fluorescence in situ hybridization, single nucleotide polymorphism arrays, and/or massively parallel sequencing (gene panel, whole exome and transcriptome sequencing) methods. We confirmed the age-associated differences in the origin of the COL1A1-PDGFB fusion and could show that it in most cases must arise after DNA synthesis, i.e., in the S or G2 phase of the cell cycle. Whereas there was a non-random pattern of secondary chromosomal rearrangements, single nucleotide variants seem to have little impact on tumor progression. No clear genomic differences between low-grade and high-grade DPFT were found, but the number of chromosomes and chromosomal imbalances as well as the frequency of 9p deletions all tended to be greater among the latter. Gene expression profiling of tumors with COL1A1-PDGFB fusions associated with unbalanced translocations or ring chromosomes identified several transcriptionally up-regulated genes in the amplified regions of chromosomes 17 and 22, including TBX2, PRKCA, MSI2, SOX9, SOX10, and PRAME.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Genetics
volume
241
pages
8 pages
publisher
Elsevier
external identifiers
  • scopus:85077145351
  • pmid:31870844
ISSN
2210-7762
DOI
10.1016/j.cancergen.2019.12.001
language
English
LU publication?
yes
additional info
Copyright © 2019. Published by Elsevier Inc.
id
e1aca203-6269-4e0b-a8e9-41577cbac985
date added to LUP
2020-01-08 12:13:15
date last changed
2021-04-06 01:53:19
@article{e1aca203-6269-4e0b-a8e9-41577cbac985,
  abstract     = {<p>The dermatofibrosarcoma protuberans family of tumors (DPFT) comprises cutaneous soft tissue neoplasms associated with aberrant PDGFBR signaling, typically through a COL1A1-PDGFB fusion. The aim of the present study was to obtain a better understanding of the chromosomal origin of this fusion and to assess the spectrum of secondary mutations at the chromosome and nucleotide levels. We thus investigated 42 tumor samples from 35 patients using chromosome banding, fluorescence in situ hybridization, single nucleotide polymorphism arrays, and/or massively parallel sequencing (gene panel, whole exome and transcriptome sequencing) methods. We confirmed the age-associated differences in the origin of the COL1A1-PDGFB fusion and could show that it in most cases must arise after DNA synthesis, i.e., in the S or G2 phase of the cell cycle. Whereas there was a non-random pattern of secondary chromosomal rearrangements, single nucleotide variants seem to have little impact on tumor progression. No clear genomic differences between low-grade and high-grade DPFT were found, but the number of chromosomes and chromosomal imbalances as well as the frequency of 9p deletions all tended to be greater among the latter. Gene expression profiling of tumors with COL1A1-PDGFB fusions associated with unbalanced translocations or ring chromosomes identified several transcriptionally up-regulated genes in the amplified regions of chromosomes 17 and 22, including TBX2, PRKCA, MSI2, SOX9, SOX10, and PRAME.</p>},
  author       = {Köster, Jan and Arbajian, Elsa and Viklund, Björn and Isaksson, Anders and Hofvander, Jakob and Haglund, Felix and Bauer, Henrik and Magnusson, Linda and Mandahl, Nils and Mertens, Fredrik},
  issn         = {2210-7762},
  language     = {eng},
  pages        = {34--41},
  publisher    = {Elsevier},
  series       = {Cancer Genetics},
  title        = {Genomic and transcriptomic features of dermatofibrosarcoma protuberans : Unusual chromosomal origin of the COL1A1-PDGFB fusion gene and synergistic effects of amplified regions in tumor development},
  url          = {http://dx.doi.org/10.1016/j.cancergen.2019.12.001},
  doi          = {10.1016/j.cancergen.2019.12.001},
  volume       = {241},
  year         = {2020},
}