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 tu mor. Whether desmoid tumor is a truly neoplastic cellular proliferativ e process or, alternatively, an unchecked reactive process has been a subject of debate. In order to determine whether desmoid tumor is comp osed of a clonal cell population as opposed to being a polyclonal reac tive process, analysis of patterns of X-chromosome inactivation was pe rformed. 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 protei nase K digestion. Following treatment with methylation sensitive restr iction 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 r eceptor (HUMARA). In eight of 12 cases, PCR amplification of the genom ic DNAs was successful? and all eight of the amplified cases were hete rozygous in the size of the HUMARA target. The remaining cases could n ot be studied because of failure to amplify DNA. Following digestion w ith Hha I or Hpa II, uniform patterns of X-chromosome inactivation wer e found in all eight desmoid tumors, whereas normal control tissue rem ained heterozygous. These results confirm a clonal composition of the tumors. The demonstration of clonality in the tumors in all eight info rmative cases indicates that desmoid tumor is a true neoplastic proces s, not an unchecked polyclonal reactive process.