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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 x 10(-7), FDR = 0.39) were identified. Strikingly, the prototypical cancer recessive genes TP53, PTEN and CDKN2A all ranked in the top 0.5% genes. The functions significantly affected by cancer mutations are exactly overlapping those of known cancer genes, with the critical exception for the absence of tyrosine kinases, as expected for a recessive gene-set.

Original publication

DOI

10.1371/journal.pone.0003380

Type

Journal article

Journal

PLoS One

Publication Date

2008

Volume

3

Keywords

Amino Acid Substitution, DNA Mutational Analysis, Databases, Nucleic Acid, Expressed Sequence Tags, Genes, Neoplasm, Genes, Recessive, Genome, Humans, Microarray Analysis, Molecular Sequence Data, Mutation, Neoplasms