CpG methylation analysis--current status of clinical assays and potential applications in molecular diagnostics: a report of the Association for Molecular Pathology.
Methylation of CpG islands in gene promoter regions is a major molecular mechanism of gene silencing and underlies both cancer development and progression. In molecular oncology, testing for the CpG methylation of tissue DNA has emerged as a clinically useful tool for tumor detection, outcome prediction, and treatment selection, as well as for assessing the efficacy of treatment with the use of demethylating agents and monitoring for tumor recurrence. In addition, because CpG methylation occurs early in pre-neoplastic tissues, methylation tests may be useful as markers of cancer risk in patients with either infectious or inflammatory conditions. The Methylation Working Group of the Clinical Practice Committee of the Association of Molecular Pathology has reviewed the current state of clinical testing in this area. We report here our summary of both the advantages and disadvantages of various methods, as well as the needs for standardization and reporting. We then conclude by summarizing the most promising areas for future clinical testing in cancer molecular diagnostics.
Sepulveda
Antonia R
AR
Methylation Working Group of the Association for Molecular Pathology Clinical Practice Committee, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Jones
Dan
D
Ogino
Shuji
S
Samowitz
Wade
W
Gulley
Margaret L
ML
Edwards
Robin
R
Levenson
Victor
V
Pratt
Victoria M
VM
Yang
Bin
B
Nafa
Khedoudja
K
Yan
Liying
L
Vitazka
Patrick
P
D000970:Antineoplastic Agents / Q000627:therapeutic use; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D004262:DNA Restriction Enzymes / Q000378:metabolism; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011401:Promoter Regions, Genetic; D011786:Quality Control; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D013447:Sulfites / Q000737:chemistry
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D013447:Sulfites; D004262:DNA Restriction Enzymes; C042345:hydrogen sulfite