Limits...
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

Analysis of mutations in the genes encoding for the four human PtdIns 4-kinases in the 852 breast cancer samples collated in the COSMIC database. (a) Over 60% of breast cancer samples have increased copy numbers of the PI4KB gene. (b) Analysis of PtdIns 4-kinase gene copy number loss and (c) frequency of point mutations in the same breast cancer samples.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4216804&req=5

Figure 1: Analysis of mutations in the genes encoding for the four human PtdIns 4-kinases in the 852 breast cancer samples collated in the COSMIC database. (a) Over 60% of breast cancer samples have increased copy numbers of the PI4KB gene. (b) Analysis of PtdIns 4-kinase gene copy number loss and (c) frequency of point mutations in the same breast cancer samples.

Mentions: PtdIns 4-kinases catalyze the phosphorylation of PtdIns to generate PtdIns4P and this is the first committed energy consuming step in the pathway that produces the signalling molecules PtdIns(4,5)P2 and PtdIns(3,4,5)P3. The initial aim of this study was to ascertain if any PtdIns 4-kinase gene was mutated in breast cancer. The COSMIC database which collates genomic sequencing results from different studies was searched, and of the four mammalian PtdIns 4-kinases only the PI4KB gene which encodes PtdIns 4-kinase IIIβ was found to be commonly mutated (Figure 1). In over 60% of the samples surveyed there was an increase in PI4KB gene copy number. Moreover, there were concomitant decreases in gene copy number for the other PtdIns 4-kinase genes indicating that in breast cancer PI4KB is the dominant PtdIns 4-kinase. Across all four human PtdIns 4-kinase genes less than 1% exhibited point mutations indicating that this type of genetic alteration was unlikely to significantly contribute to breast cancer tumourigenesis.


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

Waugh MG - J Cancer (2014)

Analysis of mutations in the genes encoding for the four human PtdIns 4-kinases in the 852 breast cancer samples collated in the COSMIC database. (a) Over 60% of breast cancer samples have increased copy numbers of the PI4KB gene. (b) Analysis of PtdIns 4-kinase gene copy number loss and (c) frequency of point mutations in the same breast cancer samples.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Analysis of mutations in the genes encoding for the four human PtdIns 4-kinases in the 852 breast cancer samples collated in the COSMIC database. (a) Over 60% of breast cancer samples have increased copy numbers of the PI4KB gene. (b) Analysis of PtdIns 4-kinase gene copy number loss and (c) frequency of point mutations in the same breast cancer samples.
Mentions: PtdIns 4-kinases catalyze the phosphorylation of PtdIns to generate PtdIns4P and this is the first committed energy consuming step in the pathway that produces the signalling molecules PtdIns(4,5)P2 and PtdIns(3,4,5)P3. The initial aim of this study was to ascertain if any PtdIns 4-kinase gene was mutated in breast cancer. The COSMIC database which collates genomic sequencing results from different studies was searched, and of the four mammalian PtdIns 4-kinases only the PI4KB gene which encodes PtdIns 4-kinase IIIβ was found to be commonly mutated (Figure 1). In over 60% of the samples surveyed there was an increase in PI4KB gene copy number. Moreover, there were concomitant decreases in gene copy number for the other PtdIns 4-kinase genes indicating that in breast cancer PI4KB is the dominant PtdIns 4-kinase. Across all four human PtdIns 4-kinase genes less than 1% exhibited point mutations indicating that this type of genetic alteration was unlikely to significantly contribute to breast cancer tumourigenesis.

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