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Pancreatic neuroendocrine tumors (pNETs) are uncommon cancers arising from pancreatic islet cells. Here we report the analysis of gene mutation, copy number, and RNA expression of 57 sporadic well-differentiated pNETs. pNET genomes are dominated by aneuploidy, leading to concordant changes in RNA expression at the level of whole chromosomes and chromosome segments. We observed two distinct patterns of somatic pNET aneuploidy that are associated with tumor pathology and patient prognosis. Approximately 26% of the patients in this series had pNETs with genomes characterized by recurrent loss of heterozygosity (LoH) of 10 specific chromosomes, accompanied by bi-allelic MEN1 inactivation and generally poor clinical outcome. Another ~40% of patients had pNETs that lacked this recurrent LoH pattern but had chromosome 11 LoH, bi-allelic MEN1 inactivation, and universally good clinical outcome. The somatic aneuploidy allowed pathogenic germline variants (e.g., ATM) to be expressed unopposed, with RNA expression patterns showing inactivation of downstream tumor suppressor pathways. No prognostic associations were found with tumor morphology, single gene mutation, or expression of RNAs reflecting the activity of immune, differentiation, proliferative or tumor suppressor pathways. In pNETs, single gene mutations appear to be less important than aneuploidy, with MEN1 the only statistically significant recurrently mutated driver gene. In addition, only one pNET in the series had clearly actionable single nucleotide variants (SNVs) (in PTEN and FLCN) confirmed by corroborating RNA expression changes. The two clinically relevant patterns of LoH described here define a novel oncogenic mechanism and a plausible route to genomic precision oncology for this tumor type.

Writer/director David Gleeson made his feature debut with coming-of-age comedy/drama Cowboys & Angels. Fans of Cowboys & Angels will fing The Front Line a very different movie. How did your experience as director of the two films compare Both were very right shoots and budgets - even though The Front Line was double the budget of Cowboys & Angels, which was produced for just over one million euro. [...]I didn't want to go the Rwanda route because it had been dealt with [e.g. in hotel Rwanda and Shooting Dogs], and also the Congo was a much more murderous campaign. Since the Second World War, no conflict has claimed more lives.

The Wind that Shakes the Barley is the story of two brothers who fight for independence only to be torn apart by the Civil War. The Wind That Shakes the Barley, whose cosy, old-fashioned title belies a savage tale of brothers-in-arms set in the War of Independence and the Civil War. A period film increases the numbers on the crew, the costumes, the special effects; the budget is much higher. Once you've engaged in war, even a just war, there's a remorseless logic and then you're damaged by it A bit of rain was quite good because it's good for the light, it gives you great kick off the land.

Trouble With Sex coincided with the Irish Film Board announcing their low-budget initiative two or three years ago. The reaction to the screening at the Dublin International Film Festival was funny. Trouble With Sex has a distinctive visual style, What kind of preparation went into that? FINTAN: Trouble with Sex is released on 6th May. www.troublewithsex.com Someone pointed out a statistic that American movies have half the number of scenes of European movies, and they've got about two-thirds of the dialogue of European movies.

First-time feature director Terry Loane fully exploits the comic potential of the plot, based on Owen McCaffeny's original stage play, Mojo Mickybo, and draws two charming, convincing performances from the pint-sized tearaways (John Joe McNeill and Niall Wright). Full marks to production designer Tom McCullagh for the period detail of the 1970s, the clothes, hairstyles, furniture, stylishly evoked here (if that isn't a contradiction), an attention you might expect given the director's CV as theatre and film set designer, his first calling. [...]the final reuniting of the runaways with their families, especially their fathers, is over-long, so drawn-out and romanticised that it loses whatever power it should have to move, and robs the ultimate betrayal of Jonjo by Mickybo of its punch.

[...]I'm far from qualified in this area but I do have a strong sense of it.' Excommunicated by the Church and censored by the State, the innovative librarian, Abbey Theatre board director, broadcaster, lecturer, critic and writer lived through the first seven decades of the 20th century, through world wars, civil wars, and through the birth of the Irish Free State. [...]I think his ideas are as interesting as his cinema.

Cut to 2002 and another opening scene, another nightclub, another vulnerable, gamine, angelic-looking girl, another outlaw male, though this one is rescuing, not avenging her. 1980s Northern Ireland has been replaced by 21st Century Nice, photographed here (by Chris Menges, who also shot Angel) in all its sophisticated, seedy allure, a subterranean swirl of gambling, drugs and trafficked girls. Two of the most unsatisfying Jordan narratives, The Miracle and In Dreams, focus on the Oedipal myth and Mona Lisa's closing image of male best friends and the daughter seems like a scene from another movie altogether, and dilutes the power of the heartbreak and disillusion George has just suffered. Sex and desire precede violence in almost every Jordan work (and look out for the colour red!) If he seems most comfortable in the twilight zone (literally in the fog and mist, with the occasional dodgy dream sequence thrown in for good measure), he is a director equally interested in performance. [...]of the Affair, the novelist Bendrix (Ralph Fiennes) also plays detective and then hires one to discover why his ex-lover ended their liaison so abruptly years before, ironically leading to further misunderstandings and misperceptions until he chances on another book, Sarah's diary.

Nolte 's performance is faultless except for one early scene of over-arch dialogue where he picks the girl, Anne, up on the road. Since the making of this film, real-life hell-raiser Nolte 's had a real-life run-in with the cops for driving under the influence (maybe, Winona-style, he was rehearsing?) The inventive plot twists and turns from the stylish, shady dangers of Nice along the heady hairpin-bends of the coast road to the upmarket glitz of Monte Carlo, the land of 'fake glamour and bad plastic surgery' Bob has a band of associates around him, in Magnificent Seuen style, of which he is undisputed kingpin, and a spectacular plan that marries music and mathematics, art and technology. Whatever about the South of France setting, this being Jordan-land there's a transvestite with a troublesome phobia since his sex-change, a male 'angel', Tony Angel, a dodgy low-life art dealer brilliantly played by Ralph Fiennes, religious references (see title for details) and a great soundtrack featuring crooning from Leonard Cohen (debauched) to Bono (cocktail smooth). For a director who loves to play with audience expectations and assumptions, Jordan is utterly in his element, dangerously close to having fun.

Watching the opening scenes of Catherine Breillat's new film, Sex Is Comedy, I couldn't help wondering why more modem film-makers aren't tempted to resort to painted moving backdrops instead of having to struggle with the great outdoors itself. The day may be clear, but the temperature is arctic, and a sudden downpour proves the last straw for the sexy encounter two young actors, a host of extras and a tense crew are trying to simulate. Here, of course, the inclement elements are a fictional device designed to provoke some of the comedy and the cruelty that runs throughout a fictional film, but they recall the actual freak floods filmed in Lost in La Mancha, this summer's documentary about ferry Gilliam's abortive attempts to shoot the feature, Don Quixote.

Since the controversial Road to God Knows Where in 1988, Alan Gilsenan has made the documentary genre his own, casting a challenging eye over AIDS, disaffected priests, and modern-day America, among others, up to the present-day sequel Road II and the Ghost of Roger Casement. Recently Gilsenan has turned to drama, with his short Zulu 9 reaping critical acclaim and his second full-length feature, shooting in Morocco in the autumn. If they continue on their current road, RTE is going to end up some sort of sub-standard digital extraterrestrial channel that nobody watches. [...]a positive aspect of the deluge of advertising and MTV that's pounding at us every day is that the audience is now sophisticated visually in terms of what it will accept.