Desmoid tumor is a clonal cellular proliferation: PCR amplification of HUMARA for analysis of patterns of X-chromosome inactivation.

Desmoid tumor is a locally aggressive, nonmetastasizing soft tissue tumor. Whether desmoid tumor is a truly neoplastic cellular proliferative process or, alternatively, an unchecked reactive process has been a subject of debate. In order to determine whether desmoid tumor is composed of a clonal cell population as opposed to being a polyclonal reactive process, analysis of patterns of X-chromosome inactivation was performed. Hematoxylin and eosin stained sections of paraffin-embedded, formalin-fixed tissues were microdissected to obtain both lesional and normal control samples, and the genomic DNAs were extracted by proteinase K digestion. Following treatment with methylation sensitive restriction endonuclease (Hha I or Hpa II), the genomic DNAs were amplified by polymerase chain reaction (PCR), using nested primers targeted to a highly polymorphic short tandem repeat (STR) of the human androgen receptor (HUMARA). In eight of 12 cases, PCR amplification of the genomic DNAs was successful, and all eight of the amplified cases were heterozygous in the size of the HUMARA target. The remaining cases could not be studied because of failure to amplify DNA. Following digestion with HhaI or Hpa II, uniform patterns of X-chromosome inactivation were found in all eight desmoid tumors, whereas normal control tissue remained heterozygous. These results confirm a clonal composition of the tumors. The demonstration of clonality in the tumors in all eight informative cases indicates that desmoid tumor is a true neoplastic process, not an unchecked polyclonal reactive process.