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Metaphases were imaged using a ZEISS AxioImager.Z2 microscope and the Metafer automated capture system (MetaSystems) ,
, DNA-FISH on metaphase spreads
A total of 1 ug of each locus-specific BAC probes were precipitated, pre-annealed, denatured and then mixed with a XCyting Mouse Chromosome 9 (Orange) paint from MetaSystems just before hybridization, Metaphases were imaged using a ZEISS AxioImagerZ.2 microscope and the Metafer automated capture system (MetaSystems), and counted manually, vol.9, pp.46653159-46855832, 2013. ,
, Lymphocyte development was analyzed in the thymus, bone marrow, lymph nodes and spleen of 4 to 8-week-old mice. All single-cell suspensions were treated with Fc-blocking antibody (CD16-32, 1:200 dilution) before cell surface staining, in phosphate-buffered saline (PBS) with 2% fetal bovine serum for 30 min at 4 C. T lineage cell populations from the thymus were identified based on the expression of the following markers: double-negative (DN) cells (CD4 -CD8 -), vol.1, p.2
, double-positive (DP) cells (CD4 + CD8 + ) and single-positive (SP) cells (CD4 + CD8 -and CD4 -CD8 + ). T cells from the spleen were identified based on the expression of CD3 + TCRb + . The following antibodies were used for cell surface staining: anti-CD4, anti-CD44 (IM7, 1:200 dilution), anti-CD25 (PC61, 1:200 dilution), anti-TCRb (H57-597,1:200 dilution) and anti-CD28 (E18, 1:200 dilution). Flow cytometry was performed on a FACS Canto II (BD Bioscience) and data were analyzed using FlowJo (TreeStar)
, DNA isolation and sequencing
, The resulting libraries were then sequenced on an Illumina HiSeq 2000 or HiSeq 2500 using a V3 or V4 flow cell generation generating two 100-or 125-bp paired-end reads. Basecalling was performed with Illumina RTA 1.18.64. Bcl conversions into Fastq were performed using bcl2fastq version 1.8.3. Tumors were sequenced with an average coverage of 36x (range = 18-52) and control samples were sequenced
Read count was calculated in sliding windows (window size was set to 50,000 bp) and control sample was used to normalize read count in the tumor sample. Copy number profiles per chromosome were visualized using R. Identification of SV Structural Variations (SV) were predicted by SVDetect (Zeitouni et al., 2010) version r0.8b, which uses discordant mapped read pairs provided by the aligner to indicate potential genomic variations from the reference. Mean insert size and standard deviation were computed using the function CollectInsertSizeMetrics from Picard tools. Discordant read pairs with low BWA-backtrack mapping quality scores (the threshold was set to 23) were removed, RNA isolation and sequencing RNA was prepared from single-cell suspensions of mouse lymphomic and healthy thymus using the RNeasy Mini Kit (QIAGEN), vol.7, 2009. ,