Comprehensive detection of recurring genomic abnormalities : a targeted sequencing approach for multiple myeloma

Recent genomic research efforts in multiple myeloma have revealed clinically relevant molecular subgroups beyond conventional cytogenetic classifications. Implementing these advances in clinical trial design and in routine patient care requires a new generation of molecular diagnostic tools. Here, we present a custom capture next-generation sequencing (NGS) panel designed to identify rearrangements involving the IGH locus, arm level, and focal copy number aberrations, as well as frequently mutated genes in multiple myeloma in a single assay. We sequenced 154 patients with plasma cell disorders and performed a head-to-head comparison with the results from conventional clinical assays, i.e., fluorescent in situ hybridization (FISH) and single-nucleotide polymorphism (SNP) microarray. Our custom capture NGS panel had high sensitivity (>99%) and specificity (>99%) for detection of IGH translocations and relevant chromosomal gains and losses in multiple myeloma. In addition, the assay was able to capture novel genomic markers associated with poor outcome such as bi-allelic events involving TP53. In summary, we show that a multiple myeloma designed custom capture NGS panel can detect IGH translocations and CNAs with very high concordance in relation to FISH and SNP microarrays and importantly captures the most relevant and recurrent somatic mutations in multiple myeloma rendering this approach highly suitable for clinical application in the modern era

The effects of a nurse case manager and a community health worker team on diabetic control, emergency department visits, and hospitalizations among urban African Americans with type 2 diabetes mellitus: a randomized controlled trial.

BACKGROUND: Although African American adults bear a disproportionate burden from diabetes mellitus (DM), few randomized controlled trials have tested culturally appropriate interventions to improve DM care. METHODS: We randomly assigned 542 African Americans with type 2 DM enrolled in an urban managed care organization to either an intensive or minimal intervention group. The intensive intervention group consisted of all components of the minimal intervention plus individualized, culturally tailored care provided by a nurse case manager (NCM) and a community health worker (CHW), using evidence-based clinical algorithms with feedback to primary care providers (eg, physicians, nurse practitioners, or physician assistants). The minimal intervention consisted of mailings and telephone calls every 6 months to remind participants about preventive screenings. Data on diabetic control were collected at baseline and at 24 months by blind observers; data emergency department (ER) visits and hospitalizations were assessed using administrative data. RESULTS: At baseline, participants had a mean age of 58 years, 73% were women, and 50% were living in poverty. At 24 months, compared with the minimal intervention group, those in the intensive intervention group were 23% less likely to have ER visits (rate difference [RD], -14.5; adjusted rate ratio [RR], 0.77; 95% confidence interval [CI], 0.59-1.00). In on-treatment analyses, the rate reduction was strongest for patients who received the most NCM and CHW visits (RD, -31.0; adjusted RR, 0.66; 95% CI, 0.43-1.00; rate reduction downward arrow 34%). CONCLUSION: These data suggest that a culturally tailored intervention conducted by an NCM/CHW team reduced ER visits in urban African Americans with type 2 DM. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00022750