**12. Conclusion**

Both DNA methylation and histone modifications play a crucial role in the maintenance of normal cell function and cellular identity of cancer cells. In breast cancer cells these epigenetic modification become massively perturbed, leading to significant changes in expression profiles which confer advantage to the development of a malignant phenotype. DNMTs are the enzymes responsible for setting up and maintaining DNA methylation patterns in eukaryotic cells. Intriguingly, DNMTs were found to be overexpressed in cancerous cells, which is believed to partly explain the hypermethylation phenomenon commonly observed in tumors. Thus, epigenetic modifications are clearly involved in breast cancer initiation and progression. Early studies focused on single genes important in prognosis and prediction, but newer genome-wide methods are identifying many genes whose regulation is epigenetically altered during breast cancer progression. Detection of hypermethylation in specific genes like RASSF1A could be used as a form of surveillance to detect early stage breast cancer, however future studies may find that the addition of multiple genes and the inclusion of histone alterations to predictive panels may improve sensitivity and specificity. In addition to the use of epigenetic alterations as a means of screening, epigenetic alterations in a tumor or adjacent tissues may also help clinicians in determining prognosis and treatment in breast cancer patients. As we understand specific epigenetic alterations contributing to breast tumorigenesis and prognosis, these discoveries will lead in future to significant advances for breast cancer treatment.

#### **13. References**


ductal carcinoma in situ) as compared with invasive breast cancers. They suggested that DNA methylation may represent an interesting target for the development of new molecular markers for the detection of breast cancer cells in tumours and bodily fluids. The most widely used analytical approach for the determination of methylation status is methylation-specific-PCR (MSP). This method is based on bisulphite conversion of unmethylated cytosin to thymidine while methylated cytosines are protected from conversion. PCR primers are designed to specifically amplify the modified methylated sequence (Hoque et al., 2009). Semiquantitative approaches which combine the advantages of MSP which is applicable and highly sensitive to any CpGs and RT-PCR were also developed and used for methylation

Both DNA methylation and histone modifications play a crucial role in the maintenance of normal cell function and cellular identity of cancer cells. In breast cancer cells these epigenetic modification become massively perturbed, leading to significant changes in expression profiles which confer advantage to the development of a malignant phenotype. DNMTs are the enzymes responsible for setting up and maintaining DNA methylation patterns in eukaryotic cells. Intriguingly, DNMTs were found to be overexpressed in cancerous cells, which is believed to partly explain the hypermethylation phenomenon commonly observed in tumors. Thus, epigenetic modifications are clearly involved in breast cancer initiation and progression. Early studies focused on single genes important in prognosis and prediction, but newer genome-wide methods are identifying many genes whose regulation is epigenetically altered during breast cancer progression. Detection of hypermethylation in specific genes like RASSF1A could be used as a form of surveillance to detect early stage breast cancer, however future studies may find that the addition of multiple genes and the inclusion of histone alterations to predictive panels may improve sensitivity and specificity. In addition to the use of epigenetic alterations as a means of screening, epigenetic alterations in a tumor or adjacent tissues may also help clinicians in determining prognosis and treatment in breast cancer patients. As we understand specific epigenetic alterations contributing to breast tumorigenesis and prognosis, these discoveries

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**15** 

*P. R. China* 

**Histone Modification and Breast Cancer** 

In eukaryotic cells, DNA is maintained in a highly ordered and condensed form via its association with small, basic histone proteins. The fundamental subunit of chromatin, the nucleosome, is composed of an octamer of four core histones, an H3/H4 tetramer and two H2A/H2B dimers, around which 146 bp of DNA are wrapped. Dynamic modulation of chromatin structure, that is, chromatin remodeling, is a key component in the regulation of gene expression, apoptosis, DNA replication and repair and chromosome condensation and segregation. Enzymes that eovalently modify histones control many cellular processes by affecting gene expression. These modifications of core histones mainly include of methylation, acetylation, phosphorylation, ubiquitination/sumoylation, ADPribosylation, deamination, and proline isomerisation (Ito, 2007; Bartova et al., 2008). The abnormal regulation of these processes is intimately associated with human diseases,

Breast cancer, the leading cause of death from cancer in women, is a heterogeneous disease ranging from premalignant hyperproliferation to invasive and metastatic carcinomas (Jemal et al., 2011). The disease progression is poorly understood but is likely due to the accumulation of genetic mutations leading to widespread changes in gene expression. Accumulating evidence has suggested that abnormal alteration of histone modification plays roles in the process of breast cancer. This chapter will summarize the relationship between histone modification and the molecular mechanism of breast cancer, and the therapy strategies focused on histone modification for breast cancer will also be

Chromatin is the physiological template of eukaryotic genome. Its fundamental unit, the nucleosome core particle, contains ~200 bp of DNA, organized by an octamer of small, basic proteins. The protein components are histones (two copies of each highly conserved core histone protein – H2A, H2B, H3 and H4). They form an interior core; the DNA lies on the surface of the particle. Nucleosomes are an invariant component of euchromatin and heterochromatin in the interphase nucleus, and of mitotic chromosomes. The nucleosome core particle represents the first level of organization, with a packing ratio of ~6. The second level of organization is the coiling of the series of nucleosomes into a helical array

**1. Introduction** 

including cancer.

discussed.

**2. Histone modification and breast cancer** 

**2.1 Chromatin structure and histone modifications** 

Xue-Gang Luo, Shu Guo, Yu Guo and Chun-Ling Zhang

*Tianjin University of Science and Technology* 

