An Utter Double Twist On Dolutegravir

To better understand the molecular pathogenesis of SS, we performed exome sequencing, copy number variation (CNV) and gene expression analysis on primary SS cells. DNA was extracted from magnetic bead-enriched peripheral blood CD4+ tumor cells from a typical patient with SS (see Appendix S1), and neutrophils from the same patient were used as matched normal cells. Exome sequencing and somatic mutation calling were performed as recently described [7]. DNA samples from nine additional patients with SS (selected CD4+ cells or MNC fraction with tumor cell percentage >35%, Table S2) were used as a screening cohort and Talazoparib ic50 samples from six patients with MF served as a control. Expression analysis was also performed on patient and healthy control peripheral blood CD4+ RNA using the Illumina Human HT-12 v4 BeadChip expression array. In CNV analysis of the exome sequencing data, the patient presented with three copies of chromosome 8, large deletions of 9q, loss of heterozygosity of 10q (including tumor suppressor PTEN) and complex rearrangement of 17q. Mutation calling from the sequencing data revealed 25 high-confidence non-synonymous somatic mutations (P-value CAPNS1 from which 11 variants were chosen for the validation by capillary sequencing based on P-value and medical relevance (Table?1). All validated variants were screened from nine additional patients with SS, but no recurrent cases were found in this small screening cohort. As a control group, six patients with MF were screened and no mutations were found in their blood samples. Among the validated variants with the lowest P-values were TBL1XR1 (T229R) and EPHA7 (G972V), both novel missense mutations converting neutral amino acids to either hydrophilic (Thr > Arg) or very hydrophobic (Gly > Val) (Fig.?1a). In addition, exome sequencing revealed four missense mutations in close vicinity of each other in the SLFN12 gene in chromosome Integrase inhibitor 17q (E261Q, M177I, E161Q, R155T) (Fig.?1b). However, based on the CNV analysis, the patient harboured a third copy of chromosome 17q making the findings difficult to validate through capillary sequencing. Altogether 35 significantly overexpressed genes (P?