© F e r r a t a S t o r t i F o u n d a t i o nUIMC1, FAM175A, BABAM1, BRE, BARD1, BRCC3 and BRCA1 and participates in DNA double-strand break (DSB) repair. 17 DSBs are associated with genomic instability, cell death 18 and carcinogenesis. 19 To repair DSBs, cells use both homologous recombination (HR), which uses sister-chromatid alleles as templates in late S and G 2 , and non-homologous end joining (NHEJ) which can operate in all phases of the cell cycle but often leaves small deletions, possibly gene inactivating at the site of repair. 20 The BRISC complex comprises the following proteins: FAM175B/ABRO1, BRCC3/BRCC36, BRE/BRCC45 and MERIT40/NBA1.Here, we report that somatic defects of BRCC3 are acquired in various myeloid neoplasms and have consequences at the cellular, and perhaps the clinical level. Methods PatientsBone marrow aspirates or blood were collected from the patients with various myeloid neoplasms seen at the Cleveland Clinic, University of Tokyo and Münchner Leukämielabor GmbH (MLL) (Online Supplementary Table S1). Informed consent for sample collection was obtained according to protocols approved by the institutional review boards in accordance with the Declaration of Helsinki. Diagnoses were confirmed according to 2008 World Health Organization classification criteria. 21 A total of 1778 patients were enrolled in this study (Online Supplementary Table S1). Next generation sequencingWhole exome sequencing (WES) was performed as previously reported. 4,6 Briefly, tumor DNAs were extracted from patients' bone marrow cells. For germ-line controls, DNA was obtained from paired CD3 + T cells. For targeted detection of sequence alterations, confirmation of WES and assessment of variant allelic frequency (VAF), we applied deep sequencing to targeted exons, as previously described. 6,22 Briefly, each targeted exon was amplified with each pair of primers, generating 200bp fragments on average. These amplicons were subjected to massive parallel sequencing (Illumina, San Diego, CA, USA) using TruSeq custom primers (Illumina) and SureSelect (Agilent, Santa Clara, CA, USA) with paired-end reads, according to the manufacture's instruction. Some of these procedures were followed by confirmation using Sanger sequencing, as previously described. 13 Annotations by NCBI reference numbers of the genes affected by somatic mutations are summarized in Online Supplementary Table S2. Cytogenetics and single nucleotide polymorphism-array analysesTechnical details about sample processing and data analyses for single nucleotide polymorphism-array (SNP-A) have been previously described.23 Affymetrix 250K and 6.0 Kit (Affymetrix) were used. Germ-line copy number variants in our internal database or in a publicly available database (Database of Genomic Variants) (http://dgv.tcag.ca/dgv/app/home) were considered non-somatic variants and excluded. Results were analyzed with CNAG (v.3.0) 24 or Genotyping Console (Affymetrix). All other lesions were confirmed as somatic or germ-line by analysis of CD3-sorted cells. Sh...

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic disorder with heterogeneous clinical, morphological and genetic characteristics. Clonal cytogenetic abnormalities are found in 20-30% of patients with CMML. Patients with low risk cytogenetic features (normal karyotype and isolated loss of Y chromosome) account for~80% of CMML patients and often fall into the low risk categories of CMML prognostic scores. We hypothesized that single nucleotide polymorphism arrays (SNP-A) karyotyping could detect cryptic chromosomal alterations with prognostic impact in these subgroup of patients. SNP-A were performed at diagnosis in 128 CMML patients with low risk karyotypes or uninformative results for conventional G-banding cytogenetics (CC). Copy number alterations (CNAs) and regions of copy number neutral loss of heterozygosity (CNN-LOH) were detected in 67% of patients. Recurrent CNAs included gains in regions 8p12 and 21q22 as well as losses in 10q21.1 and 12p13.2. Interstitial CNN-LOHs were recurrently detected in the following regions: 4q24-4q35, 7q32.1-7q36.3, and 11q13.3-11q25. Statistical analysis showed that some of the alterations detected by SNP-A associated with the patients' outcome. A shortened overall survival (OS) and progression free survival (PFS) was observed in cases where the affected size of the genome (considering CNAs and CNN-LOHs) was >11 Mb. In addition, presence of interstitial CNN-LOH was predictive of poor OS. Presence of CNAs ( ‡1) associated with poorer OS and PFS in the patients with myeloproliferative CMML. Overall, SNP-A analysis increased the diagnostic yield in patients with low risk cytogenetic features or uninformative CC and added prognostic value to this subset of patients.

Objective. To investigate barriers and correlates of the use of HIV prevention services and HIV testing behaviors among men who have sex with men in Chongqing. Methods. Three consecutive cross-sectional surveys provided demographic, sexual behavior, HIV/syphilis infection, HIV prevention service, and testing behavior data. Results. Of 1239 participants, 15.4% were infected with HIV, incidence was 12.3 per 100 persons/year (95% CI: 9.2–15.3), 38% of the participants reported ever having unprotected insertive anal sex, 40% ever received free condom/lubricants in the past year, and 27.7% ever obtained free sexually transmitted infection examination/treatment in the past year. Multivariable logistic regression revealed that lower levels of HIV/AIDS related stigmatizing/discriminatory attitudes, full-time jobs, and sex debut with men at a younger age were independently associated with use of free condom/lubricants. Large social networks, higher incomes, and sexual debut with men at a younger age were associated with use of any HIV prevention and HIV testing services. Lower levels of stigmatizing/discriminatory attitudes were also associated with HIV testing. Fearing needles and being unaware of the venues for testing were top barriers for testing service utilization. Conclusion. It is imperative to address HIV/AIDS related stigmatizing/discriminatory attitudes and other barriers while delivering intervention and testing services.