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PMID: 7856759 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A polymerase chain reaction assay for non-random X chromosome inactivation identifies monoclonal endometrial cancers and precancers.

The American journal of pathology ·Vol. 146 ·No. 2 ·1995-02-00 ·Pages 501-8

Mutter GL, Chaponot ML, Fletcher JA

Abstract

We hypothesize that endometrial carcinoma and their precursors share a monoclonal growth pattern and tested this thesis with archival paraffin-embedded tissues using a polymerase chain reaction-based assay for non-random X chromosome inactivation. Of the 10 well-differentiated endometrial adenocarcinoma cases with heterozygous markers (HUMARA, X-linked androgen receptor gene), 9 had skewed X inactivation consistent with a monoclonal process, and one contained a structurally altered HUMARA gene. X inactivation skewing similar to that of the tumor was seen in matched control polyclonal tissues of 4 (of 9) cases, caused by the small number of endometrial stem cells at the time of embryonic X inactivation. When the polymerase chain reaction assay was applied to four potential endometrial precancers (atypical endometrial hyperplasia) and matched control tissues, two were inconclusive, and two were found to be monoclonal. We conclude that 1) it is essential to include polyclonal control tissues in X inactivation analyses to determine whether skewing is a specific indicator of monoclonality; and 2) endometrial adenocarcinomas and some putative precancers, atypical endometrial hyperplasia, are monoclonal.

MeSH Terms
Adenocarcinoma/genetics,pathology Base Sequence Dosage Compensation, Genetic Endometrial Hyperplasia/genetics,pathology Endometrial Neoplasms/genetics,pathology Female Humans Molecular Sequence Data Polymerase Chain Reaction/methods Sex Chromosome Aberrations/genetics,pathology Tumor Stem Cell Assay X Chromosome
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Mutter G L
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Chaponot M L
Fletcher J A
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
Published
1995-02-00
Pages
501-8
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1869842
Subset
IM
Grants
NCI NIH HHS · R29-CA49859 · United States
External Links
PubMed source PMC Full Text View journal details
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