Gene Silencing
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Herman and Baylin (Nov. 20 issue)1 provide an excellent review of gene silencing in cancer in association with promoter hypermethylation. However, some readers who are new to the field will be confused by the introductory section of their article — in particular, the authors' explanation of the term "epigenetic," which suggests that this term describes "a heritable change in the pattern of gene expression." In fact, in this context, promoter hypermethylation is a somatic event, and although it may be passed on to daughter somatic cells, it is not heritable in the germ line. Although it is later stated that "epigenetic change is not a mechanism of the first hit" in familial cancer, the introductory summary may be misleading.
Judy Kirk, M.B., B.S.
Westmead Hospital
2145 Sydney, Australia
judy_kirk@wmi.usyd.edu.au
References
Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 2003;349:2042-2054.
The authors reply: We thank Dr. Kirk for her thoughtful comments regarding the definition of the term "epigenetic" in our review. She is certainly correct in stating that the heritable patterns defined by this term generally refer to gene-expression changes not based on changes in the DNA base sequence and that they are passed on to daughter cells in a somatic-cell, rather than a germ-cell, context. Thus, DNA-methylation patterns are heritable through cell division but are usually not hereditary in the sense of being passed on through meiosis. It should be noted, however, that there are DNA-methylation patterns, and attendant gene silencing, that are perpetuated in somatic cells from heritable marks established in the germ line according to the parental origin of alleles. This is the process of gene imprinting, wherein only one allele of a gene is expressed in somatic cells. Technically, however, the epigenetic process we review with respect to cancer cells is, as Dr. Kirk points out, a somatic-cell transmission mechanism.
James G. Herman, M.D.
Stephen B. Baylin, M.D.
Johns Hopkins Medical Institutions
Baltimore, MD 21231
sbaylin@jhmi.edu
Judy Kirk, M.B., B.S.
Westmead Hospital
2145 Sydney, Australia
judy_kirk@wmi.usyd.edu.au
References
Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 2003;349:2042-2054.
The authors reply: We thank Dr. Kirk for her thoughtful comments regarding the definition of the term "epigenetic" in our review. She is certainly correct in stating that the heritable patterns defined by this term generally refer to gene-expression changes not based on changes in the DNA base sequence and that they are passed on to daughter cells in a somatic-cell, rather than a germ-cell, context. Thus, DNA-methylation patterns are heritable through cell division but are usually not hereditary in the sense of being passed on through meiosis. It should be noted, however, that there are DNA-methylation patterns, and attendant gene silencing, that are perpetuated in somatic cells from heritable marks established in the germ line according to the parental origin of alleles. This is the process of gene imprinting, wherein only one allele of a gene is expressed in somatic cells. Technically, however, the epigenetic process we review with respect to cancer cells is, as Dr. Kirk points out, a somatic-cell transmission mechanism.
James G. Herman, M.D.
Stephen B. Baylin, M.D.
Johns Hopkins Medical Institutions
Baltimore, MD 21231
sbaylin@jhmi.edu