Genome wide identification of recessive cancer genes by combinatorial mutation analysis.

Autor: Stefano Volinia, Nicoletta Mascellani, Jlenia Marchesini, Angelo Veronese, Elizabeth Ormondroyd, Hansjuerg Alder, Jeff Palatini, Massimo Negrini, Carlo M Croce
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Zdroj: PLoS ONE, Vol 3, Iss 10, p e3380 (2008)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0003380
Popis: 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.
Databáze: Directory of Open Access Journals