title: X-inactivation patch size in human female tissue confounds the assessment of tumor clonality.
abstract: 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.
authors.affiliation: Department of Histopathology, Rockefeller Building, University Street, University College London Hospitals, London WC1E 6JJ, United Kingdom. m.novelli@ucl.ac.uk
authors.forename: Marco
authors.initials: M
authors.lastname: Novelli
authors.forename: Antonio
authors.initials: A
authors.lastname: Cossu
authors.forename: Dahmane
authors.initials: D
authors.lastname: Oukrif
authors.forename: Alberto
authors.initials: A
authors.lastname: Quaglia
authors.forename: Sunil
authors.initials: S
authors.lastname: Lakhani
authors.forename: Richard
authors.initials: R
authors.lastname: Poulsom
authors.forename: Peter
authors.initials: P
authors.lastname: Sasieni
authors.forename: Piera
authors.initials: P
authors.lastname: Carta
authors.forename: Marcella
authors.initials: M
authors.lastname: Contini
authors.forename: Anna
authors.initials: A
authors.lastname: Pasca
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmieri
authors.forename: Walter
authors.initials: W
authors.lastname: Bodmer
authors.forename: Francesco
authors.initials: F
authors.lastname: Tanda
authors.forename: Nick
authors.initials: N
authors.lastname: Wright
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001940:Breast / Q000033:anatomy & histology / Q000201:enzymology; D003106:Colon / Q000033:anatomy & histology / Q000201:enzymology; D004303:Dosage Compensation, Genetic; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007421:Intestine, Small / Q000033:anatomy & histology / Q000201:enzymology; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D017354:Point Mutation; D013961:Thyroid Gland / Q000033:anatomy & histology / Q000201:enzymology
chemical_list: D005954:Glucosephosphate Dehydrogenase