Roberto Mancini suffered defeat in the Istanbul derby as Fenerbahce beat rivals Galatasaray 2-0 to go four points clear at the top of the table.
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Former Galatasaray midfielder Emre Belozoglu opened the scoring with a 23rd-minute penalty.
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Didier Drogba threatened for Galatasaray but Cristian Baroni's 66th-minute finish sealed their fate.
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It was Galatasaray's second straight defeat after losing to FC Copenhagen in the Champions League last week.
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Galatasaray's day to forget was summed up when Felipe Melo missed a last-minute penalty.
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Former Manchester City boss Mancini had seen his side win three straight league games after losing 2-1 at Akhisar Belediyespor on 6 October.
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But defeat leaves them nine points behind Fenerbahce in the table.