Secondary Structure at a Hot Spot for DNA Methylation in DNA from Human Breast Cancers

Cancer Genomics - Proteomics

STEVEN S. SMITH¹  JARROD CLARK¹ 

[1] City of Hope, 1500 E. Duarte Rd., Duarte, CA, U.S.A. City of Hope, 1500 E. Duarte Rd., Duarte, CA, U.S.A. City of Hope, 1500 E. Duarte Rd., Duarte, CA, U.S.A.

关键词: DNA methylation;    breast cancer;    Secondary stucture;    VNTR;    c-Ha-ras;    MspI site polymorphism;   

DOI  :  

来源: Delinasios GJ CO

【 摘 要 】

The VNTR at c-Ha-ras resides in a hotspot for DNA methylation on chromosome 11 in human tumors, where it is flanked by two MspI restriction sites. We have investigated the nature of the MspI site polymorphism at the c-Ha-ras VNTR observed in variety of tumors including breast cancer. We find that the MspI site 5′ to the VNTR is present in a Non-B DNA structure with single-strand character that renders it accessible to bisulfite modification under native conditions, while the MspI site 3′ to the VNTR appears to reside in a normal B-form structure that is inaccessible to bisulfite. The non-B DNA structure accounts for the observed polymorphism since MspI cannot cleave single-stranded DNA and control experiments show that the MspI sites were neither mutated nor abnormally methylated. Southern blotting showed that structural polymorphism was present in tumor DNA and tumor adjacent normal tissue DNA but absent from lymphocyte DNA from the same patients. We conclude that the non-B DNA structural polymorphism detected in human tumors near the c-Ha-ras VNTR is a self-perpetuating epigenetic mark that manifests itself spontaneously during breast carcinogenesis in a methylation hot spot.

【 授权许可】

Unknown