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Clonal origins of human breast cancer
Author(s) -
Going James J.,
Abd ElMonem Hanan M.,
Craft John A.
Publication year - 2001
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.937
Subject(s) - biology , monoclonal , breast cancer , carcinoma , cancer research , cancer , pathology , microbiology and biotechnology , monoclonal antibody , genetics , antibody , medicine
Tumours are usually considered as the clonal progeny of single transformed cells. An X‐chromosome inactivation assay has been applied to exploring clonal relationships in human breast cancer. Analysis of X‐inactivation in DNA extracted from microdissected in situ and invasive breast carcinoma by Hpa II restriction and polymerase chain reaction (PCR) of the androgen receptor exon I CAG polymorphism confirmed monoclonality in 105/133 samples of carcinoma cells from 31/32 informative breast cancers. Clonality was identical in seven cases between in situ and invasive carcinoma. Unexpectedly, 4 of 12 cancers (33%) with two or more monoclonal samples available were mosaic (polyclonal) in respect of X‐chromosome inactivation between separate morphologically homogeneous tumour cell samples. Concordant clonality supports a common clonal origin of in situ and invasive breast cancers, but frequent apparently mosaic X‐inactivation in breast cancer cannot be explained by non‐tumour cell contamination. It is concluded that these carcinomas may be genuinely multiclonal. Possible mechanisms of multiclonality include simultaneous transformation of cell groups straddling X‐chromosome inactivation patch boundaries, tumour‐initiating mutations prior to X‐inactivation, or recruitment of bystander stem cells by DNA transfer from necrotic or apoptotic tumour cells. Collision of independent cancers appears implausible at this frequency. Further studies using independent analytical techniques are required to test the important possibility that a significant proportion of mammary carcinomas are not monoclonal. Copyright © 2001 John Wiley & Sons, Ltd.