G2Cdb::Human Disease report

Disease id
D00000107
Name
Invasive breast carcinoma
Nervous system disease
no

Genes (2)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00001624 PIK3CA
phosphoinositide-3-kinase, catalytic, alpha polypeptide
Y (15837735) Microinsertion (MI) Y
G00001473 GNAS
GNAS complex locus
Y (17186357) Single nucleotide polymorphism (SNP) Y

References

  • The T393C polymorphism in the gene GNAS1 of G protein is associated with survival of patients with invasive breast carcinoma.

    Otterbach F, Callies R, Frey UH, Schmitz KJ, Wreczycki C, Kimmig R, Siffert W and Schmid KW

    Institute of Pathology and Neuropathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45122, Essen, Germany.

    The GNAS1 locus encodes the G(alpha)s protein which stimulates the formation of cyclic AMP (cAMP). Subsequently the cAMP pathway mediates various pleiotropic effects including regulation of apoptosis and proliferation. We have recently shown that genotypes of the single nucleotide polymorphism (SNP) T393C in the gene GNAS1 are associated with survival of patients suffering from bladder, renal cell and colorectal carcinoma. In the present study, the genotypes of the T393C SNP were determined in 279 patients with invasive breast carcinoma. Comparing the genotypes with the overall survival as well as important clinico-pathological parameters showed that carriers of the T allele had a significantly less favourable course of the disease when compared to carriers of the homozygous CC genotype. In multivariate analysis the homozygous TT genotype was independently associated with a decreased overall survival. Our results suggest that the GNAS1 T393C SNP is a novel genetic host factor for disease progression in patients with invasive breast carcinoma.

    Breast cancer research and treatment 2007;105;3;311-7

  • Frequent mutation of the PIK3CA gene in ovarian and breast cancers.

    Levine DA, Bogomolniy F, Yee CJ, Lash A, Barakat RR, Borgen PI and Boyd J

    Gynecology and Breast Research Laboratory, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

    Purpose: Activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, resulting in increased cell proliferation, survival, and motility, is believed to play an oncogenic role in many cancer types. The PIK3CA gene encodes the p110alpha catalytic subunit of PI3K, and is amplified in some ovarian cancers, whereas the AKT2 gene is amplified in some ovarian, breast, and pancreatic cancers. Recently, in a mutational screen of eight PI3K genes and eight PI3K-like genes, PIK3CA was found to be the only gene affected by somatic mutations, which were observed frequently in gastrointestinal and brain cancers. Here, we test whether PIK3CA is subject to mutation in ovarian and breast cancers.

    Exons 9 and 20, encoding the highly conserved helical and kinase domains of PIK3CA, were subjected to sequence analysis in 198 advanced stage epithelial ovarian carcinomas and 72 invasive breast carcinomas (48 of ductal histology and 24 of lobular histology).

    Results: Somatic missense mutations were observed in 24 of 198 (12%) ovarian carcinomas, and in 13 of 72 (18%) breast carcinomas.

    Conclusions: These data indicate that mutations of PIK3CA play an oncogenic role in substantial fractions of ovarian and breast carcinomas, and in consideration of mutation of other components of the PI3K-AKT pathway in both tumor types, confirm the major oncogenic role of this pathway in ovarian and breast carcinomas.

    Clinical cancer research : an official journal of the American Association for Cancer Research 2005;11;8;2875-8

Literature (2)

Pubmed - human_disease

  • The T393C polymorphism in the gene GNAS1 of G protein is associated with survival of patients with invasive breast carcinoma.

    Otterbach F, Callies R, Frey UH, Schmitz KJ, Wreczycki C, Kimmig R, Siffert W and Schmid KW

    Institute of Pathology and Neuropathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45122, Essen, Germany.

    The GNAS1 locus encodes the G(alpha)s protein which stimulates the formation of cyclic AMP (cAMP). Subsequently the cAMP pathway mediates various pleiotropic effects including regulation of apoptosis and proliferation. We have recently shown that genotypes of the single nucleotide polymorphism (SNP) T393C in the gene GNAS1 are associated with survival of patients suffering from bladder, renal cell and colorectal carcinoma. In the present study, the genotypes of the T393C SNP were determined in 279 patients with invasive breast carcinoma. Comparing the genotypes with the overall survival as well as important clinico-pathological parameters showed that carriers of the T allele had a significantly less favourable course of the disease when compared to carriers of the homozygous CC genotype. In multivariate analysis the homozygous TT genotype was independently associated with a decreased overall survival. Our results suggest that the GNAS1 T393C SNP is a novel genetic host factor for disease progression in patients with invasive breast carcinoma.

    Breast cancer research and treatment 2007;105;3;311-7

Pubmed - other

  • Frequent mutation of the PIK3CA gene in ovarian and breast cancers.

    Levine DA, Bogomolniy F, Yee CJ, Lash A, Barakat RR, Borgen PI and Boyd J

    Gynecology and Breast Research Laboratory, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

    Purpose: Activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, resulting in increased cell proliferation, survival, and motility, is believed to play an oncogenic role in many cancer types. The PIK3CA gene encodes the p110alpha catalytic subunit of PI3K, and is amplified in some ovarian cancers, whereas the AKT2 gene is amplified in some ovarian, breast, and pancreatic cancers. Recently, in a mutational screen of eight PI3K genes and eight PI3K-like genes, PIK3CA was found to be the only gene affected by somatic mutations, which were observed frequently in gastrointestinal and brain cancers. Here, we test whether PIK3CA is subject to mutation in ovarian and breast cancers.

    Exons 9 and 20, encoding the highly conserved helical and kinase domains of PIK3CA, were subjected to sequence analysis in 198 advanced stage epithelial ovarian carcinomas and 72 invasive breast carcinomas (48 of ductal histology and 24 of lobular histology).

    Results: Somatic missense mutations were observed in 24 of 198 (12%) ovarian carcinomas, and in 13 of 72 (18%) breast carcinomas.

    Conclusions: These data indicate that mutations of PIK3CA play an oncogenic role in substantial fractions of ovarian and breast carcinomas, and in consideration of mutation of other components of the PI3K-AKT pathway in both tumor types, confirm the major oncogenic role of this pathway in ovarian and breast carcinomas.

    Clinical cancer research : an official journal of the American Association for Cancer Research 2005;11;8;2875-8

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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