Patients with chronic lymphocytic leukaemia and clonal deletion of both 17p13.1 and 11q22.3 have a very poor prognosis.

Detection of a 17p13.1 deletion (loss of TP53) or 11q22.3 deletion (loss of ATM), by fluorescence in situ hybridization (FISH), in chronic lymphocytic leukaemia (CLL) patients is associated with a poorer prognosis. Because TP53 and ATM are integral to the TP53 pathway, we hypothesized that 17p13.1- (17p-) and 11q22.3- (11q-) occurring in the same cell (clonal 17p-/11q-) would confer a worse prognosis than either 17p- or 11q-. We studied 2184 CLL patients with FISH (1995-2012) for the first occurrence of 17p-, 11q-, or clonal 17p-/11q-. Twenty (1%) patients had clonal 17p-/11q-, 158 (7%) had 17p- (including 4 with 17p- and 11q- in separate clones), 247 (11%) had 11q-, and 1759 (81%) had neither 17p- nor 11q-. Eleven of 15 (73%) tested patients with clonal 17p-/11q- had dysfunctional TP53 mutations. Overall survival for clonal 17p-/11q- was significantly shorter (1·9 years) than 17p- (3·1 years, P = 0·04), 11q- (4·8 years, P ≤ 0·0001), or neither 17p- nor 11q- (9·3 years, P ≤ 0·0001). Clonal 17p-/11q- thus conferred significantly worse prognosis, suggesting that loss of at least one copy of both TP53 and ATM causes more aggressive disease. Use of an ATM/TP53 combination FISH probe set could identify these very-high risk patients.

The Mayo Clinic Biobank: a building block for individualized medicine.

OBJECTIVE: To report the design and implementation of the first 3 years of enrollment of the Mayo Clinic Biobank. PATIENTS AND METHODS: Preparations for this biobank began with a 4-day Deliberative Community Engagement with local residents to obtain community input into the design and governance of the biobank. Recruitment, which began in April 2009, is ongoing, with a target goal of 50,000. Any Mayo Clinic patient who is 18 years or older, able to consent, and a US resident is eligible to participate. Each participant completes a health history questionnaire, provides a blood sample, and allows access to existing tissue specimens and all data from their Mayo Clinic electronic medical record. A community advisory board provides ongoing advice and guidance on complex decisions. RESULTS: After 3 years of recruitment, 21,736 individuals have enrolled. Fifty-eight percent (12,498) of participants are female and 95% (20,541) of European ancestry. Median participant age is 62 years. Seventy-four percent (16,171) live in Minnesota, with 42% (9157) from Olmsted County, where the Mayo Clinic in Rochester, Minnesota, is located. The 5 most commonly self-reported conditions are hyperlipidemia (8979, 41%), hypertension (8174, 38%), osteoarthritis (6448, 30%), any cancer (6224, 29%), and gastroesophageal reflux disease (5669, 26%). Among patients with self-reported cancer, the 5 most common types are nonmelanoma skin cancer (2950, 14%), prostate cancer (1107, 12% in men), breast cancer (941, 4%), melanoma (692, 3%), and cervical cancer (240, 2% in women). Fifty-six percent (12,115) of participants have at least 15 years of electronic medical record history. To date, more than 60 projects and more than 69,000 samples have been approved for use. CONCLUSION: The Mayo Clinic Biobank has quickly been established as a valuable resource for researchers.

Light exposure among adolescents with delayed sleep phase disorder: a prospective cohort study.

The objective of this study was to compare light exposure and sleep parameters between adolescents with delayed sleep phase disorder (DSPD; n=16, 15.3±1.8 yrs) and unaffected controls (n=22, 13.7±2.4 yrs) using a prospective cohort design. Participants wore wrist actigraphs with photosensors for 14 days. Mean hourly lux levels from 20:00 to 05:00 h and 05:00 to 14:00 h were examined, in addition to the 9-h intervals prior to sleep onset and after sleep offset. Sleep parameters were compared separately, and were also included as covariates within models that analyzed associations with specified light intervals. Additional covariates included group and school night status. Adolescent delayed sleep phase subjects received more evening (p< .02, 22:00-02:00 h) and less morning (p .05, 08:00-09:00 h and 10:00-12:00 h) light than controls, but had less pre-sleep exposure with adjustments for the time of sleep onset (p< .03, 5-7 h prior to onset hour). No differences were identified with respect to the sleep offset interval. Increased total sleep time and later sleep offset times were associated with decreased evening (p< .001 and p= .02, respectively) and morning (p= .01 and p< .001, respectively) light exposure, and later sleep onset times were associated with increased evening exposure (p< .001). Increased total sleep time also correlated with increased exposure during the 9 h before sleep onset (p= .01), and a later sleep onset time corresponded with decreased light exposure during the same interval (p< .001). Outcomes persisted regardless of school night status. In conclusion, light exposure interpretation requires adjustments for sleep timing among adolescents with DSPD. Pre- and post-sleep light exposures do not appear to contribute directly to phase delays. Sensitivity to morning light may be reduced among adolescents with DSPD.