X-inactivation patch size in human female tissue confounds the assessment of tumor clonality
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ICR Authors
Authors
Novelli, M
Cossu, A
Oukrif, D
Quaglia, A
Lakhani, S
Poulsom, R
Sasieni, P
Carta, P
Contini, M
Pasca, A
Palmieri, G
Bodmer, W
Tanda, F
Wright, N
Cossu, A
Oukrif, D
Quaglia, A
Lakhani, S
Poulsom, R
Sasieni, P
Carta, P
Contini, M
Pasca, A
Palmieri, G
Bodmer, W
Tanda, F
Wright, N
Document Type
Journal Article
Date
2003-03-18
Date Accepted
Abstract
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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)
<jats:italic>Biochim. Biophys. Acta</jats:italic>
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)
<jats:italic>Science</jats:italic>
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.
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Citation
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 pp. 3311 - 3314
Source Title
Publisher
Proceedings of the National Academy of Sciences
ISSN
0027-8424
eISSN
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Research Team
Molecular Pathology