Recurrent Chromosomal Copy Number Alterations in Sporadic Chordomas

The molecular events in chordoma pathogenesis have not been fully delineated, particularly with respect to copy number changes. Understanding copy number alterations in chordoma may reveal critical disease mechanisms that could be exploited for tumor classification and therapy. We report the copy number analysis of 21 sporadic chordomas using array comparative genomic hybridization (CGH). Recurrent copy changes were further evaluated with immunohistochemistry, methylation specific PCR, and quantitative real-time PCR. Similar to previous findings, large copy number losses, involving chromosomes 1p, 3, 4, 9, 10, 13, 14, and 18, were more common than copy number gains. Loss of CDKN2A with or without loss of CDKN2B on 9p21.3 was observed in 16/20 (80%) unique cases of which six (30%) showed homozygous deletions ranging from 76 kilobases to 4.7 megabases. One copy loss of the 10q23.31 region which encodes PTEN was found in 16/20 (80%) cases. Loss of CDKN2A and PTEN expression in the majority of cases was not attributed to promoter methylation. Our sporadic chordoma cases did not show hotspot point mutations in some common cancer gene targets. Moreover, most of these sporadic tumors are not associated with T (brachyury) duplication or amplification. Deficiency of CDKN2A and PTEN expression, although shared across many other different types of tumors, likely represents a key aspect of chordoma pathogenesis. Sporadic chordomas may rely on mechanisms other than copy number gain if they indeed exploit T/ brachyury for proliferation

The Binding of Religious Heroes in Andreas and the Hêliand

Scholarly approaches to the Old English Andreas have tended to emphasise the poem's formulaic debt to Beowulf and the works of Cynewulf, but as of yet unexplored is its strikingly similar use of the binding motif also present in the Old Saxon alliterative gospel, the Hêliand. These two poems, likely produced in a similar period, share not only a depiction of bound religious heroes that far outstrips their sources, but also specific formulaic and linguistic parallels. The suggestion that the Hêliand's preoccupation with the binding of Christ stems directly from the experience of those Saxons subjugated by the Franks is, therefore, problematised when we take into account the formulaic nature of binding terminology in the closely related language of Old English. Similarly, a desire to read the binding of the saints in Andreas as a unique innovation does not take into account the possibility that the poet may have been familiar with a tradition in which Christ's Passion includes binding. In discussing these two texts together, this paper emphasises a cross-cultural interest in bondage, as well as the importance of exploring formulaic connections between the Old English and Old Saxon corpora