X-inactivation patch size in human female tissue confounds the assessment of tumor clonality
AUTOR(ES)
Novelli, Marco
FONTE
The National Academy of Sciences
RESUMO
Most models of tumorigenesis assume that tumors are monoclonal in origin. This conclusion is based largely on studies using X chromosome-linked markers in females. One important factor, often ignored in such studies, is the distribution of X-inactivated cells in tissues. Because lyonization occurs early in development, many of the progeny of a single embryonic stem cell are grouped together in the adult, forming patches. As polyclonality can be demonstrated only at the borders of X-inactivation patches, the patch size is crucial in determining the chance of demonstrating polyclonality and hence the number of tumors that need to be examined to exclude polyclonality. Previously studies using X-linked genes such as glucose-6-phosphate dehydrogenase have been handicapped by the need to destroy the tissues to study the haplotypes of glucose-6-phosphate dehydrogenase [Fialkow, P.-J. (1976) Biochim. Biophys. Acta 458, 283–321] or to determine the restriction fragment length polymorphisms of X chromosome-linked genes [Vogelstein, B., Fearon, E. R., Hamilton, S. R. & Feinberg, A. P. (1985) Science 227, 642–645]. Here we visualize X-inactivation patches in human females directly. Results show that the patch size is relatively large in both the human colon and breast, confounding assessment of tumor clonality with traditional X-inactivation studies.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=152288Documentos Relacionados
- A first-generation X-inactivation profile of the human X chromosome
- Clonality of CD3 negative large granular lymphocyte proliferations determined by PCR based X-inactivation studies.
- Comparative Sequence and X-Inactivation Analyses of a Domain of Escape in Human Xp11.2 and the Conserved Segment in Mouse
- Influence of Gene Duplication and X-Inactivation on Mouse Mitochondrial Malic Enzyme Activity and Electrophoretic Patterns
- Xist Yeast Artificial Chromosome Transgenes Function as X-Inactivation Centers Only in Multicopy Arrays and Not as Single Copies