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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

Histogram demonstrating the distribution of copy number increases in individual breast tumours for each of the amplified phosphoinositide pathway genes identified.
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Figure 4: Histogram demonstrating the distribution of copy number increases in individual breast tumours for each of the amplified phosphoinositide pathway genes identified.

Mentions: To further analyse the degree to which these genes were amplified in each breast cancer case, the copy number status of each gene was investigated in individual patient samples (Figure 4). These results showed that gene copy number amplification for this pathway ranged from 3 -16 additional copies but that for most tumours the range was 3 - 6 extra copies. Since gene copy number increases can arise from either an increase in ploidy - a common event associated with multinucleation in many cancers, or from numerical increases in specific chromosomes, a more stringent algorithm was employed in order to minimize the contribution of copy number variation caused solely by changes to complete genome duplication. Application of these more rigorous thresholds revealed that all four genes of interest were amplified in approximately 10% of breast cancer samples (10% for PI4KB, 11.4% for AKT3, 11.3% for PIK3C2B and 10.2% for PIP5K1A). These values are consistent with copy number co-amplification arising from numerical increases to chromosome 1q and not solely by mitotic defects leading to genome duplication.


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

Waugh MG - J Cancer (2014)

Histogram demonstrating the distribution of copy number increases in individual breast tumours for each of the amplified phosphoinositide pathway genes identified.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: Histogram demonstrating the distribution of copy number increases in individual breast tumours for each of the amplified phosphoinositide pathway genes identified.
Mentions: To further analyse the degree to which these genes were amplified in each breast cancer case, the copy number status of each gene was investigated in individual patient samples (Figure 4). These results showed that gene copy number amplification for this pathway ranged from 3 -16 additional copies but that for most tumours the range was 3 - 6 extra copies. Since gene copy number increases can arise from either an increase in ploidy - a common event associated with multinucleation in many cancers, or from numerical increases in specific chromosomes, a more stringent algorithm was employed in order to minimize the contribution of copy number variation caused solely by changes to complete genome duplication. Application of these more rigorous thresholds revealed that all four genes of interest were amplified in approximately 10% of breast cancer samples (10% for PI4KB, 11.4% for AKT3, 11.3% for PIK3C2B and 10.2% for PIP5K1A). These values are consistent with copy number co-amplification arising from numerical increases to chromosome 1q and not solely by mitotic defects leading to genome duplication.

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