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PIK3CA

Thursday 9 September 2004

Definition: PI3K subunit p110alpha (PIK3CA) is a subunit of PI3Ks. The phosphatidylinositol 3-kinases (PI3Ks) are known regulators of cellular growth and proliferation.

Pathology

PI3KCA is one of the most commonly mutated oncogenes in human cancer.

- somatic mutations in PIK3CA gene (kinase domain ++) in:

  • colorectal adenocarcinoma
  • mammary carcinomas (25%) (#15254419#)
  • gastric adenocarcinoma (#15784156#)
  • ovarian carcinomas
  • diffuse large B cell lymphoma (DLBCL) (#18382359#)
  • superficial papillary bladder tumors. (#16885334#)
    • PIK3CA mutations are an early genetic alteration associated with FGFR3 mutations in superficial papillary bladder tumors. (#16885334#)

- PIK3CA mutations in the helical domain (in exon 9) and in the kinase domain (exon 20) cause tumor formation by different means.

  • PIK3CA kinase domain mutation identifies a subgroup of stage III colon cancer patients with poor prognosis. (#21830111#)
  • PIK3CA mutation in exon 20 is a negative prognostic factor in stage III colon cancer patients. Moreover, this negative effect is not present in stage I and II patients. (#21830111#)

- mammary carcinomas (breast cancer) (#21830111#)

  • The PI3K-Akt cascade is a key signaling pathway involved in cell proliferation, survival, and growth.
  • Activating PIK3CA mutations have been reported in breast carcinoma (BC).
  • PIK3CA mutations are significantly associated with ER+ in HER2-negative cases. (#21830111#)
  • A higher frequency of PIK3CA mutations is present in lobular carcinoma compared with ductal carcinoma (50% vs. 35%). (#21830111#)
  • There is no association between the survival and PIK3CA mutational status. (#21830111#)
  • In hereditary BC, PIK3CA mutations are found only in the BRCA2 group.
  • The PIK3CA mutation seems to characterize the luminal-type BC, in both sporadic and BRCA2 mutated forms, and is absent in the basal-type BC, in both the sporadic and BRCA1 mutated forms. (#21830111#)

References

- Mutations of the PIK3CA gene in diffuse large B cell lymphoma. Baohua Y, Xiaoyan Z, Tiecheng Z, Tao Q, Daren S. Diagn Mol Pathol. 2008 Sep;17(3):159-65. PMID: #18382359#

- PIK3CA kinase domain mutation identifies a subgroup of stage III colon cancer patients with poor prognosis. FariƱa Sarasqueta A, Zeestraten EC, van Wezel T, van Lijnschoten G, van Eijk R, Dekker JW, Kuppen PJ, Goossens-Beumer IJ, Lemmens VE, van de Velde CJ, Rutten HJ, Morreau H, van den Brule AJ. Cell Oncol (Dordr). 2011 Dec;34(6):523-31. PMID: #21830111#

- PIK3CA in breast carcinoma: a mutational analysis of sporadic and hereditary cases. Michelucci A, Di Cristofano C, Lami A, Collecchi P, Caligo A, Decarli N, Leopizzi M, Aretini P, Bertacca G, Porta RP, Ricci S, Della Rocca C, Stanta G, Bevilacqua G, Cavazzana A. Diagn Mol Pathol. 2009 Dec;18(4):200-5. PMID: #19861897#

- Lopez-Knowles E, Hernandez S, Malats N, Kogevinas M, Lloreta J, Carrato A, Tardon A, Serra C, Real FX. PIK3CA mutations are an early genetic alteration associated with FGFR3 mutations in superficial papillary bladder tumors. Cancer Res. 2006 Aug 1;66(15):7401-4. PMID: #16885334#

- Samuels Y, Diaz LA Jr, Schmidt-Kittler O, Cummins JM, Delong L, Cheong I, Rago C, Huso DL, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE. Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell. 2005 Jun;7(6):561-73. PMID: #15950905#