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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
- Publication Year :
- 2020
- Publisher :
- Uppsala universitet, Science for Life Laboratory, SciLifeLab, 2020.
-
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 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.
- Subjects :
- Adult
G2 Phase
Male
Cancer Research
Skin Neoplasms
Adolescent
Oncogene Proteins, Fusion
Chromosomes, Human, Pair 22
Ring chromosome
Chromosomal translocation
Biology
Young Adult
03 medical and health sciences
0302 clinical medicine
Translocation mechanisms
Genetics
Dermatofibrosarcoma protuberans
medicine
Humans
Child
Fusion
Molecular Biology
Aged
Skin
Medicinsk genetik
Cancer och onkologi
medicine.diagnostic_test
Gene Expression Profiling
Dermatofibrosarcoma
Infant
Chromosome
Karyotype
Genomics
Middle Aged
medicine.disease
Gene Expression Regulation, Neoplastic
SNP-array
Child, Preschool
030220 oncology & carcinogenesis
Cancer and Oncology
COL1A1/PDGFB Fusion Gene
Female
RNA-seq
Medical Genetics
Chromosomes, Human, Pair 17
SNP array
Fluorescence in situ hybridization
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....9ea65d3b30c36a123519fd71b981063e