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Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the digestive tract, are believed to arise from the interstitial cells of Cajal. GISTs are characterized by mutations in the proto-oncogene KIT that lead to constitutive activation of its tyrosine kinase activity. The tyrosine kinase inhibitor STI571, active against the BCR-ABL fusion protein in chronic myeloid leukemia, was recently shown to be highly effective in GISTs. We used 13,826-element cDNA microarrays to define the expression patterns of 13 KIT mutation-positive GISTs and compared them with the expression profiles of a group of spindle cell tumors from locations outside the gastrointestinal tract. Our results showed a remarkably distinct and uniform expression profile for all of the GISTs. In particular, hierarchical clustering of a subset of 113 cDNAs placed all of the GIST samples into one branch, with a Pearson correlation >0.91. This homogeneity suggests that the molecular pathogenesis of a GIST results from expansion of a clone that has acquired an activating mutation in KIT without the extreme genetic instability found in the common epithelial cancers. The results provide insight into the histogenesis of GIST and the clinical behavior of this therapeutically responsive tumor.

Mortality in 11 secular kibbutzim between 1970 and 1985 was nearly twice that of 11 matched religious kibbutzim. A cross-sectional study was undertaken in 1991 in 10 of these settlements, 5 religious and 5 secular, to determine whether differences in risk factors could explain the unequal survival. These comprised physical, physiologic and biochemical measurements, health-relevant behaviors and psychosocial variables. This report addresses the psychosocial aspect of the study, which included assessment of sense of coherence, hostility, satisfaction with self, work-related stress, social supports and social contacts using self-administered questionnaires. The response rate among the sample of men and women, aged 35-64 years, was 76% (437 respondents, 208 men and 229 women). Analysis of variance and logistic regression (the latter comparing the upper or lower fourths of the distribution vs. the rest) were used. Religious kibbutz members reported a higher sense of coherence (odds ratio = 1.58, 95% CI 1.02 to 2.46) and a lower level of hostility (odds ratio = 0.49, 95% CI 0.33 to 0.75) than their secular counterparts. Findings for satisfaction with self and work-related stress were inconsistent; there were significant interactions between religious affiliation, sex and age. Younger women reported less satisfaction with self and higher work-related stress than the other age-sex groups in both types of kibbutz. There was no difference in social support or frequency of social contact between religious and secular kibbutzim. Voluntary work was more frequent among the religious kibbutzim. The findings are consistent with an interpretation that Jewish religious observance may enhance the formation of certain protective personality characteristics. Membership in a cohesive religious kibbutz community may increase host resistance to stressors and thereby promote overall well-being and a positive health status. This could reflect an interplay of individual and collective attributes of religion.