title: PIK3CA cancer mutations display gender and tissue specificity patterns.
abstract: The occurrence of oncogenic alleles can display striking tissue specificity. For example KRAS mutations are very frequent in pancreatic cancers but relatively rare in melanomas. The opposite is true for BRAF mutations. Somatic mutations in the gene encoding for the phosphatidylinositol 3-kinase (PI3KCA) catalytic subunit, PIK3CA, occur at high frequency in many solid cancers. We have examined whether PI3K oncogenic mutations (exons 9 and 20) might exhibit gender and/or tissue specificity. By examining large cohorts of breast and colorectal cancers affecting both men and women we found that the pattern of PIK3CA mutations is distinctive. In colorectal cancers, PIK3CA (but not KRAS, APC, or TP53) mutations display a gender bias occurring at higher frequencies in women. We also found that male breast cancers display PIK3CA mutations at an overall frequency similar to that observed in female breast tumors. In male breast cancers, however, PIK3CA mutations are found mainly in exon 20. We conclude that PI3KCA mutations affecting exons 9 and 20 display gender- and tissue-specific patterns, thus suggesting that the different amino acid changes could exert distinct functional effects on the oncogenic properties of this enzyme. Furthermore, we propose that sexual dimorphisms and tissue specific factors might directly or indirectly influence the occurrence of PI3KCA cancer alleles.
authors.affiliation: Laboratory of Molecular Genetics, The Oncogenomics Center, Institute for Cancer Research and Treatment (IRCC), University of Torino Medical School, Candiolo, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Benvenuti
authors.forename: Milo
authors.initials: M
authors.lastname: Frattini
authors.forename: Sabrina
authors.initials: S
authors.lastname: Arena
authors.forename: Carlo
authors.initials: C
authors.lastname: Zanon
authors.forename: Vera
authors.initials: V
authors.lastname: Cappelletti
authors.forename: Danila
authors.initials: D
authors.lastname: Coradini
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Daidone
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
authors.forename: Marco A
authors.initials: MA
authors.lastname: Pierotti
authors.forename: Alberto
authors.initials: A
authors.lastname: Bardelli
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009928:Organ Specificity; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D012727:Sex Characteristics
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human