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X-inactivation patch size in human female tissue confounds the assessment of tumor clonality

Novelli, Marco and Cossu, Antonio and Oukrif, Dahmane and Quaglia, Alberto and Lakhani, Sunil and Poulsom, Richard and Sasieni, Peter and Carta, Piera and Contini, Marcella and Pasca, Anna and Palmieri, Giuseppe and Bodmer, Walter and Tanda, Francesco and Wright, Nick (2003) X-inactivation patch size in human female tissue confounds the assessment of tumor clonality. Proceedings of The National Academy of Sciences, Vol. 100 (6), p. 3311-3314. eISSN 1091-6490. Article.

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DOI: 10.1073/pnas.0437825100


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 Xlinked 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 chromosomelinked 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.

Item Type:Article
ID Code:1134
Uncontrolled Keywords:X-inactivation patch, tumor clonality, monoclonality, polyclonality
Subjects:Area 06 - Scienze mediche > MED/06 Oncologia medica
Divisions:001 Università di Sassari > 03 Istituti > Anatomia patologica
002 Altri enti e centri di ricerca del Nord Sardegna > Azienda ASL1, Sassari > Servizio di anatomia patologica
002 Altri enti e centri di ricerca del Nord Sardegna > CNR-Consiglio Nazionale delle Ricerche > Istituto di genetica delle popolazioni, Alghero
Publisher:The National Academy of Sciences of the USA
Publisher Policy:Depositato per gentile concessione dell'Editore. È vietato duplicare e postare il PDF. E' consentito l'uso a solo scopo di studio e di ricerca.
Deposited On:18 Aug 2009 10:04

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