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Amplification of Chromosome 1q Genes Encoding the Phosphoinositide Signalling Enzymes PI4KB, AKT3, PIP5K1A and PI3KC2B in Breast Cancer.

Waugh MG - J Cancer (2014)

Bottom Line: Point mutations in the phosphatidylinositol 4-kinase genes were uncommon and appeared in less than 1% of the patient samples however, 62% of the tumours had increases in gene copy number for PI4KB which encodes the phosphatidylinositol 4-kinase IIIbeta isozyme.Extending this analysis to subsequent enzymes in the phosphoinositide signalling cascades revealed that the only PIP5K1A, PI3KC2B and AKT3 genes exhibited similar patterns of gene copy number variation.By comparison, gene copy number increases for established oncogenes such as EGFR and HER2/Neu were only evident in 20% of the samples.

View Article: PubMed Central - PubMed

Affiliation: Lipid and Membrane Biology Group, Institute for Liver and Digestive Health, UCL, Royal Free Campus, Rowland Hill Street, London, NW3 2PF United Kingdom.

ABSTRACT
Little is known about the possible oncogenic roles of genes encoding for the phosphatidylinositol 4-kinases, a family of enzymes that regulate an early step in phosphoinositide signalling. To address this issue, the mutational status of all four human phosphatidylinositol 4-kinases genes was analyzed across 852 breast cancer samples using the COSMIC data resource. Point mutations in the phosphatidylinositol 4-kinase genes were uncommon and appeared in less than 1% of the patient samples however, 62% of the tumours had increases in gene copy number for PI4KB which encodes the phosphatidylinositol 4-kinase IIIbeta isozyme. Extending this analysis to subsequent enzymes in the phosphoinositide signalling cascades revealed that the only PIP5K1A, PI3KC2B and AKT3 genes exhibited similar patterns of gene copy number variation. By comparison, gene copy number increases for established oncogenes such as EGFR and HER2/Neu were only evident in 20% of the samples. The PI4KB, PIP5K1A, PI3KC2B and AKT3 genes are related in that they all localize to chromosome 1q which is often structurally and numerically abnormal in breast cancer. These results demonstrate that a gene quartet encoding a potential phosphoinositide signalling pathway is amplified in a subset of breast cancers.

No MeSH data available.


Related in: MedlinePlus

Prevalence of high level gene copy number increases for PI4KB, AKT3, PIP5K1A and PIK3C2B in a range of cancers affecting different tissues. The data were derived from the COSMIC V70. The number of patient samples used for each analysis is given in brackets after the tissue name. Breast refers to invasive breast carcinoma, ovary to ovarian serous cyst adenocarcinoma, kidney to clear cell carcinoma, endometrium to uterine corpus endometrial cancer, large intestine to colon adenocarcinoma and lung to lung adenocarcinoma.
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Figure 5: Prevalence of high level gene copy number increases for PI4KB, AKT3, PIP5K1A and PIK3C2B in a range of cancers affecting different tissues. The data were derived from the COSMIC V70. The number of patient samples used for each analysis is given in brackets after the tissue name. Breast refers to invasive breast carcinoma, ovary to ovarian serous cyst adenocarcinoma, kidney to clear cell carcinoma, endometrium to uterine corpus endometrial cancer, large intestine to colon adenocarcinoma and lung to lung adenocarcinoma.

Mentions: To ascertain whether amplification of this gene quartet occurs in cancers affecting tissues other than breast, an assessment of copy number variation across multiple tissues was performed (Figure 5). From this analysis it was clear that co-amplification of PI4KB/PIPK1A/AKT3/PIK3C2B was most pronounced for breast carcinoma but also occurred in about 5% of endometrial cancers, lung adenocarcinomas and ovarian cancer. Mutations in these four genes were also found more rarely in less than 1% of cancers affecting the large intestine and kidney. These results demonstrate that amplification of this gene set is most commonly detected in invasive breast carcinoma but can also be found in other malignancies but at much lower frequencies.


Amplification of Chromosome 1q Genes Encoding the Phosphoinositide Signalling Enzymes PI4KB, AKT3, PIP5K1A and PI3KC2B in Breast Cancer.

Waugh MG - J Cancer (2014)

Prevalence of high level gene copy number increases for PI4KB, AKT3, PIP5K1A and PIK3C2B in a range of cancers affecting different tissues. The data were derived from the COSMIC V70. The number of patient samples used for each analysis is given in brackets after the tissue name. Breast refers to invasive breast carcinoma, ovary to ovarian serous cyst adenocarcinoma, kidney to clear cell carcinoma, endometrium to uterine corpus endometrial cancer, large intestine to colon adenocarcinoma and lung to lung adenocarcinoma.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4216804&req=5

Figure 5: Prevalence of high level gene copy number increases for PI4KB, AKT3, PIP5K1A and PIK3C2B in a range of cancers affecting different tissues. The data were derived from the COSMIC V70. The number of patient samples used for each analysis is given in brackets after the tissue name. Breast refers to invasive breast carcinoma, ovary to ovarian serous cyst adenocarcinoma, kidney to clear cell carcinoma, endometrium to uterine corpus endometrial cancer, large intestine to colon adenocarcinoma and lung to lung adenocarcinoma.
Mentions: To ascertain whether amplification of this gene quartet occurs in cancers affecting tissues other than breast, an assessment of copy number variation across multiple tissues was performed (Figure 5). From this analysis it was clear that co-amplification of PI4KB/PIPK1A/AKT3/PIK3C2B was most pronounced for breast carcinoma but also occurred in about 5% of endometrial cancers, lung adenocarcinomas and ovarian cancer. Mutations in these four genes were also found more rarely in less than 1% of cancers affecting the large intestine and kidney. These results demonstrate that amplification of this gene set is most commonly detected in invasive breast carcinoma but can also be found in other malignancies but at much lower frequencies.

Bottom Line: Point mutations in the phosphatidylinositol 4-kinase genes were uncommon and appeared in less than 1% of the patient samples however, 62% of the tumours had increases in gene copy number for PI4KB which encodes the phosphatidylinositol 4-kinase IIIbeta isozyme.Extending this analysis to subsequent enzymes in the phosphoinositide signalling cascades revealed that the only PIP5K1A, PI3KC2B and AKT3 genes exhibited similar patterns of gene copy number variation.By comparison, gene copy number increases for established oncogenes such as EGFR and HER2/Neu were only evident in 20% of the samples.

View Article: PubMed Central - PubMed

Affiliation: Lipid and Membrane Biology Group, Institute for Liver and Digestive Health, UCL, Royal Free Campus, Rowland Hill Street, London, NW3 2PF United Kingdom.

ABSTRACT
Little is known about the possible oncogenic roles of genes encoding for the phosphatidylinositol 4-kinases, a family of enzymes that regulate an early step in phosphoinositide signalling. To address this issue, the mutational status of all four human phosphatidylinositol 4-kinases genes was analyzed across 852 breast cancer samples using the COSMIC data resource. Point mutations in the phosphatidylinositol 4-kinase genes were uncommon and appeared in less than 1% of the patient samples however, 62% of the tumours had increases in gene copy number for PI4KB which encodes the phosphatidylinositol 4-kinase IIIbeta isozyme. Extending this analysis to subsequent enzymes in the phosphoinositide signalling cascades revealed that the only PIP5K1A, PI3KC2B and AKT3 genes exhibited similar patterns of gene copy number variation. By comparison, gene copy number increases for established oncogenes such as EGFR and HER2/Neu were only evident in 20% of the samples. The PI4KB, PIP5K1A, PI3KC2B and AKT3 genes are related in that they all localize to chromosome 1q which is often structurally and numerically abnormal in breast cancer. These results demonstrate that a gene quartet encoding a potential phosphoinositide signalling pathway is amplified in a subset of breast cancers.

No MeSH data available.


Related in: MedlinePlus