Similar Datasets
Project description:Cancer genomes are characterized by the accumulation of small-scale somatic mutations as well as large-scale chromosomal deletions, amplifications, and complex structural rearrangements. This characteristic is at least partially dependent on the ability of cancer cells to undergo recurrent chromosome breakage. In order to address the extent to which chromosomal structural rearrangement breakpoints correlate with recurrent DNA double-strand breaks (DSBs), we simultaneously mapped chromosome structural variation breakpoints (using whole-genome DNA-seq) and spontaneous DSB formation (using Break-seq) in the estrogen receptor (ER)-positive breast cancer cell line MCF-7 and a non-cancer control breast epithelium cell line MCF-10A. We identified concurrent DSBs and structural variation breakpoints almost exclusively in the pericentromeric region of chromosome 16q in MCF-7 cells. We fine-tuned the identification of copy number variation breakpoints on 16q. In addition, we detected recurrent DSBs that occurred in both MCF-7 and MCF-10A. We propose a model for DSB-driven chromosome rearrangements that lead to the translocation of 16q, likely with 10q, and the eventual 16q loss that does not involve the pericentromere of 16q. We present evidence from RNA-seq data that select genes, including SHCBP1, ORC6, and MYLK3, which are immediately downstream from the 16q pericentromere, show heightened expression in MCF-7 cell line compared to the control. Data published by The Cancer Genome Atlas show that all three genes have increased expression in breast tumor samples. We found that SHCBP1 and ORC6 are both strong poor prognosis and treatment outcome markers in the ER-positive breast cancer cohort. We suggest that these genes are potential oncogenes for breast cancer progression. The search for tumor suppressor loss that accompanies the 16q loss ought to be augmented by the identification of potential oncogenes that gained expression during chromosomal rearrangements.
| S-EPMC9319013 | biostudies-literature
Project description:Cancer genomes are characterized by accumulation of small-scale somatic mutations as well as large-scale chromosomal deletions, amplifications, and complex structural rearrangements. This characteristic is at least partially dependent on the ability of cancer cells to undergo recurrent chromosome breakage. In order to address to what extent chromosomal structural rearrangement breakpoints correlate with recurrent DNA double strand breaks (DSBs), we simultaneously mapped chromosome structural variation breakpoints by whole genome DNA-seq and spontaneous DSB formation by Break-seq in the breast cancer cell line MCF-7 and a non-cancer control cell line MCF-10A. We identified concurrent DSBs and structural variation breakpoints almost exclusively in the pericentromeric region of chromosome 16q in MCF-7 cells. We fine-tuned the identification of copy number variation breakpoints on 16q. In addition, we detected recurrent DSBs that occurred in both MCF-7 and MCF-10A. We propose a model for DSB-driven chromosome rearrangements that led to the translocation of 16q, likely with 10q, and the eventual 16q loss that does not involve the pericentromere of 16q. We present evidence from RNA-seq data that select genes, including SHCBP1, ORC6 and MYLK3, which are immediately downstream from the 16q pericentromere show heightened expression in MCF-7 cell line compared to the control. Data published by The Cancer Genome Atlas showed that all three genes have increased expression in breast tumor samples. We suggest that these genes are potential oncogenes for breast cancer progression. The search for tumor suppressor loss that accompanies the 16q loss ought to be augmented by the identification of potential oncogenes that gained expression during chromosomal rearrangements.
2022-07-12 | GSE207714 | GEO
Project description:Cancer genomes are characterized by accumulation of small-scale somatic mutations as well as large-scale chromosomal deletions, amplifications, and complex structural rearrangements. This characteristic is at least partially dependent on the ability of cancer cells to undergo recurrent chromosome breakage. In order to address to what extent chromosomal structural rearrangement breakpoints correlate with recurrent DNA double strand breaks (DSBs), we simultaneously mapped chromosome structural variation breakpoints by whole genome DNA-seq and spontaneous DSB formation by Break-seq in the breast cancer cell line MCF-7 and a non-cancer control cell line MCF-10A. We identified concurrent DSBs and structural variation breakpoints almost exclusively in the pericentromeric region of chromosome 16q in MCF-7 cells. We fine-tuned the identification of copy number variation breakpoints on 16q. In addition, we detected recurrent DSBs that occurred in both MCF-7 and MCF-10A. We propose a model for DSB-driven chromosome rearrangements that led to the translocation of 16q, likely with 10q, and the eventual 16q loss that does not involve the pericentromere of 16q. We present evidence from RNA-seq data that select genes, including SHCBP1, ORC6 and MYLK3, which are immediately downstream from the 16q pericentromere show heightened expression in MCF-7 cell line compared to the control. Data published by The Cancer Genome Atlas showed that all three genes have increased expression in breast tumor samples. We suggest that these genes are potential oncogenes for breast cancer progression. The search for tumor suppressor loss that accompanies the 16q loss ought to be augmented by the identification of potential oncogenes that gained expression during chromosomal rearrangements.
2022-07-12 | GSE207697 | GEO
Project description:Cancer genomes are characterized by accumulation of small-scale somatic mutations as well as large-scale chromosomal deletions, amplifications, and complex structural rearrangements. This characteristic is at least partially dependent on the ability of cancer cells to undergo recurrent chromosome breakage. In order to address to what extent chromosomal structural rearrangement breakpoints correlate with recurrent DNA double strand breaks (DSBs), we simultaneously mapped chromosome structural variation breakpoints by whole genome DNA-seq and spontaneous DSB formation by Break-seq in the breast cancer cell line MCF-7 and a non-cancer control cell line MCF-10A. We identified concurrent DSBs and structural variation breakpoints almost exclusively in the pericentromeric region of chromosome 16q in MCF-7 cells. We fine-tuned the identification of copy number variation breakpoints on 16q. In addition, we detected recurrent DSBs that occurred in both MCF-7 and MCF-10A. We propose a model for DSB-driven chromosome rearrangements that led to the translocation of 16q, likely with 10q, and the eventual 16q loss that does not involve the pericentromere of 16q. We present evidence from RNA-seq data that select genes, including SHCBP1, ORC6 and MYLK3, which are immediately downstream from the 16q pericentromere show heightened expression in MCF-7 cell line compared to the control. Data published by The Cancer Genome Atlas showed that all three genes have increased expression in breast tumor samples. We suggest that these genes are potential oncogenes for breast cancer progression. The search for tumor suppressor loss that accompanies the 16q loss ought to be augmented by the identification of potential oncogenes that gained expression during chromosomal rearrangements.
2022-07-12 | GSE207696 | GEO
Project description:Identification of recurrent chromosome breaks underlying structural rearrangements in mammary cancer cell lines
| PRJNA856867 | ENA
Project description:Identification of recurrent chromosome breaks underlying structural rearrangements in mammary cancer cell lines [RNA-seq]
| PRJNA856705 | ENA
Project description:Identification of recurrent chromosome breaks underlying structural rearrangements in mammary cancer cell lines [DNA-seq]
| PRJNA856704 | ENA
Project description:Identification of recurrent chromosome breaks underlying structural rearrangements in mammary cancer cell lines [Break-seq]
| PRJNA856873 | ENA
Project description:MotivationHigh plasticity of bacterial genomes is provided by numerous mechanisms including horizontal gene transfer and recombination via numerous flanking repeats. Genome rearrangements such as inversions, deletions, insertions, and duplications may independently occur in different strains, providing parallel adaptation or phenotypic diversity. Specifically, such rearrangements might be responsible for virulence, antibiotic resistance, and antigenic variation. However, identification of such events requires laborious manual inspection and verification of phyletic pattern consistency.ResultsHere we define the term "parallel rearrangements" as events that occur independently in phylogenetically distant bacterial strains and present a formalization of the problem of parallel rearrangements calling. We implement an algorithmic solution for the identification of parallel rearrangements in bacterial populations as a tool PaReBrick. The tool takes a collection of strains represented as a sequence of oriented synteny blocks and a phylogenetic tree as input data. It identifies rearrangements, tests them for consistency with a tree, and sorts the events by their parallelism score. The tool provides diagrams of the neighbors for each block of interest, allowing the detection of horizontally transferred blocks or their extra copies and the inversions in which copied blocks are involved.We demonstrated PaReBrick's efficiency and accuracy and showed its potential to detect genome rearrangements responsible for pathogenicity and adaptation in bacterial genomes.AvailabilityPaReBrick is written in Python and is available on GitHub https://github.com/ctlab/parallelrearrangements.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC8723149 | biostudies-literature
Project description:Chromosome 16 is one of the most gene-rich chromosomes of our genome, and 10% of its sequence consists of segmental duplications, which give instability and predisposition to rearrangement by the recurrent mechanism of non-allelic homologous recombination. Microarray technologies have allowed for the analysis of copy number variations (CNVs) that can contribute to the risk of developing complex diseases. By array comparative genomic hybridization (CGH) screening of 1476 patients, we detected 27 cases with CNVs on chromosome 16. We identified four smallest regions of overlapping (SROs): one at 16p13.11 was found in seven patients; one at 16p12.2 was found in four patients; two close SROs at 16p11.2 were found in twelve patients; finally, six patients were found with atypical rearrangements. Although phenotypic variability was observed, we identified a male bias for Childhood Apraxia of Speech associated to 16p11.2 microdeletions. We also reported an elevated frequency of second-site genomic alterations, supporting the model of the second hit to explain the clinical variability associated with CNV syndromes. Our goal was to contribute to the building of a chromosome 16 disease-map based on disease susceptibility regions. The role of the CNVs of chromosome 16 was increasingly made clear in the determination of developmental delay. We also found that in some cases a second-site CNV could explain the phenotypic heterogeneity by a simple additive effect or a pejorative synergistic effect.
| S-EPMC6429492 | biostudies-literature