Genomic characteristics and clinical significance of CD56+ circulating tumor cells in small cell lung cancer.

Circulating tumor cells (CTC) have been studied in various solid tumors but clinical utility of CTC in small cell lung cancer (SCLC) remains unclear. The aim of the CTC-CPC study was to develop an EpCAM-independent CTC isolation method allowing isolation of a broader range of living CTC from SCLC and decipher their genomic and biological characteristics. CTC-CPC is a monocentric prospective non-interventional study including treatment-naïve newly diagnosed SCLC. CD56+ CTC were isolated from whole blood samples, at diagnosis and relapse after first-line treatment and submitted to whole-exome-sequencing (WES). Phenotypic study confirms tumor lineage and tumorigenic properties of isolated cells for the 4 patients analyzed with WES. WES of CD56+ CTC and matched tumor biopsy reveal genomic alteration frequently impaired in SCLC. At diagnosis CD56+ CTC were characterized by a high mutation load, a distinct mutational profile and a unique genomic signature, compared to match tumors biopsies. In addition to classical pathways altered in SCLC, we found new biological processes specifically affected in CD56+ CTC at diagnosis. High numeration of CD56+ CTC (> 7/ml) at diagnosis was associated with ES-SCLC. Comparing CD56+ CTC isolated at diagnosis and relapse, we identify differentially altered oncogenic pathways (e.g. DLL3 or MAPK pathway). We report a versatile method of CD56+ CTC detection in SCLC. Numeration of CD56+ CTC at diagnosis is correlated with disease extension. Isolated CD56+ CTC are tumorigenic and show a distinct mutational profile. We report a minimal gene set as a unique signature of CD56+ CTC and identify new affected biological pathways enriched in EpCAM-independent isolated CTC in SCLC.

[Locomotor and cardiorespiratory impairments after retirement in relation to certain occupational exposures during working life]. / Déficiences locomotrice et cardiorespiratoire après la retraite en relation avec certaines expositions professionnelles durant la vie active.

The relationships between locomotor and cardiorespiratory impairments and occupational exposures during working life were examined, using a sample of 627 retired persons in the greater Paris area. Among men, there was a significant statistical association between carrying heavy weights and locomotor impairment. There were also significant associations between exposure to toxic products, tiring postures and vibrations and cardiorespiratory impairment among men. Concerning women, associations between exposure to dust and tiring postures during working life and cardiorespiratory impairment were observed. These results were obtained after adjusting for age, socio-professional status, tobacco use, living alone and after adjusting also for the other occupational exposures. These results are compatible with the hypothesis of long-term effects of occupational exposures on the principal health characteristics of the aged.

[Impairments, disabilities and handicaps in a group of retired people in the Paris metropolitan area in relation to their socio-occupational status]. / Déficience, incapacité et handicap dans un groupe de retraités de la Région Parisienne en relation avec la catégorie socio-professionnelle.

Interviewers using a questionnaire carried out a home survey among 627 retired persons (62.7% of the sample) in the greater Paris area for the purpose of exploring relationships between disablement (impairments, disabilities, and handicaps) and socio-professional status. The subjects were randomly selected from a pension fund roll. Among men, manual laborers had higher rates of disablement than did white-collar employees and executives. Among women, laborers, office workers and those in the services had similar disablement rates, while rates among executive women were lower. Overall, women had higher rates than men. But no relationship between age and disablement was observed. The examination of disablement indicates that socioeconomic differences--earlier shown to exist with regard to mortality and morbidity--also have their effect in retirement.