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Genome Wide Identification of Recessive Cancer Genes by Combinatorial Mutation Analysis
Authors:Stefano Volinia   Nicoletta Mascellani   Jlenia Marchesini   Angelo Veronese   Elizabeth Ormondroyd   Hansjuerg Alder   Jeff Palatini   Massimo Negrini     Carlo M. Croce
Abstract:We devised a novel procedure to identify human cancer genes acting in a recessive manner. Our strategy was to combine the contributions of the different types of genetic alterations to loss of function: amino-acid substitutions, frame-shifts, gene deletions. We studied over 20,000 genes in 3 Gigabases of coding sequences and 700 array comparative genomic hybridizations. Recessive genes were scored according to nucleotide mismatches under positive selective pressure, frame-shifts and genomic deletions in cancer. Four different tests were combined together yielding a cancer recessive p-value for each studied gene. One hundred and fifty four candidate recessive cancer genes (p-value<1.5×10−7, FDR
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