Cancer epigenomics: implications of DNA methylation in personalized cancer therapy.
Genetic alterations in cancer can provide information for predicting a tumor's sensitivity to chemotherapeutic drugs. But although such information is certainly useful, the relatively low frequency of mutations seen in many cancers limits the utility of pharmacogenomics in large numbers of cancer patients, necessitating consideration of other approaches. Epigenetic changes such as DNA methylation are a hallmark of human cancers. Methylation of genes involved in DNA repair and maintaining genome integrity (e.g. MGMT, hMLH1, WRN, and FANCF), and cell-cycle checkpoint genes (e.g. CHFR and 14-3-3 sigma, CDK10, and p73), all reportedly influence the sensitivity to chemotherapeutic drugs, suggesting that DNA methylation could serve as a molecular marker for predicting the responsiveness of tumors to chemotherapy. However, the comprehensive study of pharmacoepigenomics awaits the advent of genome-wide analysis of DNA methylation using microarrays and next-generation sequencers.
Toyota
Minoru
M
Department of Biochemistry, Cancer Research Institute, Sapporo Medical University, Sapporo 060-8556, Japan. mtoyota@sapmed.ac.jp
Suzuki
Hiromu
H
Yamashita
Toshiharu
T
Hirata
Koichi
K
Imai
Kohzoh
K
Tokino
Takashi
T
Shinomura
Yasuhisa
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000235:genetics*; D016678:Genome / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D010548:Personal Health Services
D000970:Antineoplastic Agents