Showing papers by "Mark D. Johnson published in 2013"

Functional genomic analysis of chromosomal aberrations in a compendium of 8000 cancer genomes

Abstract: A large database of copy number profiles from cancer genomes can facilitate the identification of recurrent chromosomal alterations that often contain key cancer-related genes. It can also be used to explore low-prevalence genomic events such as chromothripsis. In this study, we report an analysis of 8227 human cancer copy number profiles obtained from 107 array comparative genomic hybridization (CGH) studies. Our analysis reveals similarity of chromosomal arm-level alterations among developmentally related tumor types as well as a number of co-occurring pairs of arm-level alterations. Recurrent (“pan-lineage”) focal alterations identified across diverse tumor types show an enrichment of known cancer-related genes and genes with relevant functions in cancer-associated phenotypes (e.g., kinase and cell cycle). Tumor type-specific (“lineage-restricted”) alterations and their enriched functional categories were also identified. Furthermore, we developed an algorithm for detecting regions in which the copy number oscillates rapidly between fixed levels, indicative of chromothripsis. We observed these massive genomic rearrangements in 1%–2% of the samples with variable tumor type-specific incidence rates. Taken together, our comprehensive view of copy number alterations provides a framework for understanding the functional significance of various genomic alterations in cancer genomes.

Prevalence and factors associated with asymptomatic gonococcal and chlamydial infection among US Navy and Marine Corps men infected with the HIV: a cohort study.

Abstract: Objectives: Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) can facilitate transmission of HIV. Men who have sex with men (MSM) may harbour infections at genital and extragenital sites. Data regarding extragenital GC and CT infections in military populations are lacking. We examined the prevalence and factors associated with asymptomatic GC and CT infection among this category of HIV-infected military personnel. Design: Cross-sectional cohort study (pilot). Setting: Infectious diseases clinic at a single military treatment facility in San Diego, CA. Participants: Ninety-nine HIV-positive men were evaluated—79% men who had sex with men, mean age 31 years, 36% black and 33% married. Inclusion criteria: male, HIV-infected, Department of Defense beneficiary. Exclusion criteria: any symptom related to the urethra, pharynx or rectum. Primary outcome measures: GC and CT screening results. Results: Twenty-four per cent were infected with either GC or CT. Rectal swabs were positive in 18% for CT and 3% for GC; pharynx swabs were positive in 8% for GC and 2% for CT. Only one infection was detected in the urine (GC). Anal sex (p=0.04), male partner (OR 7.02, p=0.04) and sex at least once weekly (OR 3.28, p=0.04) were associated with infection. Associated demographics included age <35 years (OR 6.27, p=0.02), non-Caucasian ethnicity (p=0.03), <3 years since HIV diagnosis (OR 2.75, p=0.04) and previous sexually transmitted infection (STI) (OR 5.10, p=0.001). Conclusions: We found a high prevalence of extragenital GC/CT infection among HIV-infected military men. Only one infection was detected in the urine, signalling the need for aggressive three-site screening of MSM. Clinicians should be aware of the high prevalence in order to enhance health through comprehensive STI screening practices.