Publications

Over the past 30 years, Israel has made great progress in attitudes and practices about smoking; probably nothing else has contributed more to the health of its population. Yet, a recent survey about a non-smoking ban at an Israeli health sciences campus found incomplete enforcement. In addition, smoking rates among health sciences students, though lower than the general population, were higher than might be expected based on rates in other developed countries. Whether the ban is-as the authors speculate-"an intrusive life style intervention" or a justifiable public health intervention, cuts to the heart of the history of tobacco control efforts and their opposition by the tobacco industry. Despite concerns that the Israeli population is not ready to accept smoke-free bans, experience in other countries suggests otherwise.

Recent studies have detailed the genomic landscape of primary endometrial cancers, but the evolution of these cancers into metastases has not been characterized. We performed whole-exome sequencing of 98 tumor biopsies including complex atypical hyperplasias, primary tumors and paired abdominopelvic metastases to survey the evolutionary landscape of endometrial cancer. We expanded and reanalyzed The Cancer Genome Atlas (TCGA) data, identifying new recurrent alterations in primary tumors, including mutations in the estrogen receptor cofactor gene NRIP1 in 12% of patients. We found that likely driver events were present in both primary and metastatic tissue samples, with notable exceptions such as ARID1A mutations. Phylogenetic analyses indicated that the sampled metastases typically arose from a common ancestral subclone that was not detected in the primary tumor biopsy. These data demonstrate extensive genetic heterogeneity in endometrial cancers and relative homogeneity across metastatic sites.