Mass Homozygotes Accumulation in the NCI-60 Cancer Cell Lines As Compared to HapMap Trios, and Relation to Fragile Site Location

Runs of homozygosity (ROH) represents extended length of homozygotes on a long genomic distance. In oncology, it is known as loss of heterozygosity (LOH) if identified exclusively in cancer cell rather than in matched control cell. Studies have identified several genomic regions which show consistent ROH in different kinds of carcinoma. To query whether this consistency can be observed on broader spectrum, both in more cancer types and in wider genomic regions, we investigated ROH patterns in the National Cancer Institute 60 cancer cell line panel (NCI-60) and HapMap Caucasian healthy trio families. Using results from Affymetrix 500 K SNP arrays, we report a genome wide significant association of ROH regions between the NCI-60 and HapMap samples, with much a higher level of ROH (11 fold) in the cancer cell lines. Analysis shows that more severe ROH found in cancer cells appears to be the extension of existing ROH in healthy state. In the HapMap trios, the adult subgroup had a slightly but significantly higher level (1.02 fold) of ROH than did the young subgroup. For several ROH regions we observed the co-occurrence of fragile sites (FRAs). However, FRA on the genome wide level does not show a clear relationship with ROH regions

Continuous deep sedation and homicide: an unsolved problem in law and professional morality

When a severely suffering dying patient is deeply sedated, and this sedated condition is meant to continue until his death, the doctor involved often decides to abstain from artificially administering fluids. For this dual procedure almost all guidelines require that the patient should not have a life expectancy beyond a stipulated maximum of days (4–14). The reason obviously is that in case of a longer life-expectancy the patient may die from dehydration rather than from his lethal illness. But no guideline tells us how we should describe the dual procedure in case of a longer life-expectancy. Many arguments have been advanced why we should not consider it to be a form of homicide, that is, ending the life of the patient (with or without his request). I argue that none of these arguments, taken separately or jointly, is persuasive. When a commission, even one that is not itself life-shortening, foreseeably renders a person unable to undo the life-shortening effects of another, simultaneous omission, the commission and the omission together should be acknowledged to kill her. I discuss the legal and ethical implications of this conclusion